Skip to main content

Advertisement

Log in

Overlapping migratory mechanisms between neural progenitor cells and brain tumor stem cells

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

Neural stem cells present in the subventricular zone (SVZ), the largest neurogenic niche of the mammalian brain, are able to self-renew as well as generate neural progenitor cells (NPCs). NPCs are highly migratory and traverse the rostral migratory stream (RMS) to the olfactory bulb, where they terminally differentiate into mature interneurons. NPCs from the SVZ are some of the few cells in the CNS that migrate long distances during adulthood. The migratory process of NPCs is highly regulated by intracellular pathway activation and signaling from the surrounding microenvironment. It involves modulation of cell volume, cytoskeletal rearrangement, and isolation from compact extracellular matrix. In malignant brain tumors including high-grade gliomas, there are cells called brain tumor stem cells (BTSCs) with similar stem cell characteristics to NPCs but with uncontrolled cell proliferation and contribute to tumor initiation capacity, tumor progression, invasion, and tumor maintenance. These BTSCs are resistant to chemotherapy and radiotherapy, and their presence is believed to lead to tumor recurrence at distal sites from the original tumor location, principally due to their high migratory capacity. BTSCs are able to invade the brain parenchyma by utilizing many of the migratory mechanisms used by NPCs. However, they have an increased ability to infiltrate the tight brain parenchyma and utilize brain structures such as myelin tracts and blood vessels as migratory paths. In this article, we summarize recent findings on the mechanisms of cellular migration that overlap between NPCs and BTSCs. A better understanding of the intersection between NPCs and BTSCs will to provide a better comprehension of the BTSCs’ invasive capacity and the molecular mechanisms that govern their migration and eventually lead to the development of new therapies to improve the prognosis of patients with malignant gliomas.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Lois C, Alvarez-Buylla A (1994) Long-distance neuronal migration in the adult mammalian brain. Science 264(5162):1145–1148

    Article  CAS  PubMed  Google Scholar 

  2. Obernier K, Alvarez-Buylla A (2019) Neural stem cells: origin, heterogeneity and regulation in the adult mammalian brain. Development 146(4):dev156059

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Doetsch F, Garcia-Verdugo JM, Alvarez-Buylla A (1997) Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J Neurosci 17(13):5046–5061

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Sawamoto K et al (2006) New neurons follow the flow of cerebrospinal fluid in the adult brain. Science 311(5761):629–632

    Article  CAS  PubMed  Google Scholar 

  5. Del Bigio MR (2010) Ependymal cells: biology and pathology. Acta Neuropathol 119(1):55–73

    Article  PubMed  Google Scholar 

  6. Johanson C et al (2011) The distributional nexus of choroid plexus to cerebrospinal fluid, ependyma and brain: toxicologic/pathologic phenomena, periventricular destabilization, and lesion spread. Toxicol Pathol 39(1):186–212

    Article  PubMed  Google Scholar 

  7. Mirzadeh Z et al (2008) Neural stem cells confer unique pinwheel architecture to the ventricular surface in neurogenic regions of the adult brain. Cell Stem Cell 3(3):265–278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Shen Q et al (2004) Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells. Science 304(5675):1338–1340

    Article  CAS  PubMed  Google Scholar 

  9. Lim DA, Alvarez-Buylla A (2016) The Adult Ventricular-Subventricular Zone (V–SVZ) and Olfactory Bulb (OB) Neurogenesis. Cold Spring Harb Perspect Biol 8(5):a018820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ponti G et al (2013) Cell cycle and lineage progression of neural progenitors in the ventricular–subventricular zones of adult mice. Proc Natl Acad Sci USA 110(11):E1045–E1054

    Article  PubMed  PubMed Central  Google Scholar 

  11. Lois C, Garcia-Verdugo JM, Alvarez-Buylla A (1996) Chain migration of neuronal precursors. Science 271(5251):978–981

    Article  CAS  PubMed  Google Scholar 

  12. Emsley JG, Hagg T (2003) alpha6beta1 integrin directs migration of neuronal precursors in adult mouse forebrain. Exp Neurol 183(2):273–285

    Article  CAS  PubMed  Google Scholar 

  13. Martoncikova M et al (2014) Astrocytic and vascular scaffolding for neuroblast migration in the rostral migratory stream. Curr Neurovasc Res 11(4):321–329

    Article  CAS  PubMed  Google Scholar 

  14. Musah-Eroje A, Watson S (2019) A novel 3D in vitro model of glioblastoma reveals resistance to temozolomide which was potentiated by hypoxia. J Neurooncol 2019:1–10

    Google Scholar 

  15. Reeve RL et al (2017) Quiescent Oct4(+) neural stem cells (NSCs) repopulate ablated glial fibrillary acidic Protein(+) NSCs in the adult mouse brain. Stem Cells 35(9):2071–2082

    Article  CAS  PubMed  Google Scholar 

  16. Buono KD et al (2012) Leukemia inhibitory factor is essential for subventricular zone neural stem cell and progenitor homeostasis as revealed by a novel flow cytometric analysis. Dev Neurosci 34(5):449–462

    Article  CAS  PubMed  Google Scholar 

  17. Kim EJ et al (2011) Ascl1 (Mash1) defines cells with long-term neurogenic potential in subgranular and subventricular zones in adult mouse brain. PLoS One 6(3):e18472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kim JB et al (2009) Oct4-induced pluripotency in adult neural stem cells. Cell 136(3):411–419

    Article  CAS  PubMed  Google Scholar 

  19. Wang J et al (2008) c-Myc is required for maintenance of glioma cancer stem cells. PLoS One 3(11):e3769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Riddick G et al (2017) A core regulatory circuit in glioblastoma stem cells links MAPK activation to a transcriptional program of neural stem cell identity. Sci Rep 7:43605

    Article  PubMed  PubMed Central  Google Scholar 

  21. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676

    Article  CAS  PubMed  Google Scholar 

  22. Papapetrou EP (2016) Induced pluripotent stem cells, past and future. Science 353(6303):991–992

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Capela A, Temple S (2002) LeX/ssea-1 is expressed by adult mouse CNS stem cells, identifying them as nonependymal. Neuron 35(5):865–875

    Article  PubMed  Google Scholar 

  24. Mao XG et al (2009) Brain tumor stem-like cells identified by neural stem cell marker CD15. Transl Oncol 2(4):247–257

    Article  PubMed  PubMed Central  Google Scholar 

  25. Brown DV et al (2017) Expression of CD133 and CD44 in glioblastoma stem cells correlates with cell proliferation, phenotype stability and intra-tumor heterogeneity. PLoS One 12(2):e0172791

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Singh SK et al (2004) Identification of human brain tumour initiating cells. Nature 432(7015):396–401

    Article  CAS  PubMed  Google Scholar 

  27. Uchida N et al (2000) Direct isolation of human central nervous system stem cells. Proc Natl Acad Sci USA 97(26):14720–14725

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Ayanlaja AA et al (2017) Distinct features of doublecortin as a marker of neuronal migration and its implications in cancer cell mobility. Front Mol Neurosci 10:199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Doetsch F et al (2002) EGF converts transit-amplifying neurogenic precursors in the adult brain into multipotent stem cells. Neuron 36(6):1021–1034

    Article  CAS  PubMed  Google Scholar 

  30. Pang LY, Saunders L, Argyle DJ (2017) Epidermal growth factor receptor activity is elevated in glioma cancer stem cells and is required to maintain chemotherapy and radiation resistance. Oncotarget 8(42):72494–72512

    Article  PubMed  PubMed Central  Google Scholar 

  31. Guichet P-O et al (2016) Asymmetric distribution of GFAP in glioma multipotent cells. PLoS One 11(3):e0151274

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Liu X et al (2006) GFAP-expressing cells in the postnatal subventricular zone display a unique glial phenotype intermediate between radial glia and astrocytes. Glia 54(5):394–410

    Article  PubMed  Google Scholar 

  33. Iacopino F et al (2014) Isolation of cancer stem cells from three human glioblastoma cell lines: characterization of two selected clones. PLoS One 9(8):e105166

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Kaneko Y et al (2000) Musashi1: an evolutionally conserved marker for CNS progenitor cells including neural stem cells. Dev Neurosci 22(1–2):139–153

    Article  CAS  PubMed  Google Scholar 

  35. Jin X et al (2013) Cell surface Nestin is a biomarker for glioma stem cells. Biochem Biophys Res Commun 433(4):496–501

    Article  CAS  PubMed  Google Scholar 

  36. Amoureux MC et al (2010) Polysialic acid neural cell adhesion molecule (PSA-NCAM) is an adverse prognosis factor in glioblastoma, and regulates olig2 expression in glioma cell lines. BMC Cancer 10:91

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Hutton SR, Pevny LH (2011) SOX2 expression levels distinguish between neural progenitor populations of the developing dorsal telencephalon. Dev Biol 352(1):40–47

    Article  CAS  PubMed  Google Scholar 

  38. Song WS et al (2016) Sox2, a stemness gene, regulates tumor-initiating and drug-resistant properties in CD133-positive glioblastoma stem cells. J Chin Med Assoc 79(10):538–545

    Article  PubMed  Google Scholar 

  39. Khan Z et al (2013) The complexity of identifying cancer stem cell biomarkers. Cancer Invest 31(6):404–411

    Article  CAS  PubMed  Google Scholar 

  40. Guerrero-Cazares H et al (2011) Cytoarchitecture of the lateral ganglionic eminence and rostral extension of the lateral ventricle in the human fetal brain. J Comp Neurol 519(6):1165–1180

    Article  PubMed  Google Scholar 

  41. Sanai N et al (2011) Corridors of migrating neurons in the human brain and their decline during infancy. Nature 478(7369):382–386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Curtis MA et al (2007) Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension. Science 315(5816):1243–1249

    Article  CAS  PubMed  Google Scholar 

  43. Sanai N et al (2007) Comment on “Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension”. Science 318(5849):393 author reply 393

    Article  CAS  PubMed  Google Scholar 

  44. Quinones-Hinojosa A et al (2006) Cellular composition and cytoarchitecture of the adult human subventricular zone: a niche of neural stem cells. J Comp Neurol 494(3):415–434

    Article  PubMed  Google Scholar 

  45. Sanai N et al (2004) Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration. Nature 427(6976):740–744

    Article  CAS  PubMed  Google Scholar 

  46. Capilla-Gonzalez V et al (2015) Regulation of subventricular zone-derived cells migration in the adult brain. Adv Exp Med Biol 853:1–21

    Article  CAS  PubMed  Google Scholar 

  47. Quinones-Hinojosa A, Chaichana K (2007) The human subventricular zone: a source of new cells and a potential source of brain tumors. Exp Neurol 205(2):313–324

    Article  PubMed  Google Scholar 

  48. Lee JH et al (2018) Human glioblastoma arises from subventricular zone cells with low-level driver mutations. Nature 560(7717):243–247

    Article  CAS  PubMed  Google Scholar 

  49. Ostrom QT et al (2018) CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2011–2015. Neuro Oncol 20(suppl_4):iv1–iv86

    Article  PubMed  PubMed Central  Google Scholar 

  50. Wesseling P, Capper D (2018) WHO 2016 classification of gliomas. Neuropathol Appl Neurobiol 44(2):139–150

    Article  CAS  PubMed  Google Scholar 

  51. Thakkar JP et al (2014) Epidemiologic and molecular prognostic review of glioblastoma. Cancer Epidemiol Biomarkers Prev 23(10):1985–1996

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Stupp R et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996

    Article  CAS  PubMed  Google Scholar 

  53. Osuka S, Van Meir EG (2017) Overcoming therapeutic resistance in glioblastoma: the way forward. J Clin Invest 127(2):415–426

    Article  PubMed  PubMed Central  Google Scholar 

  54. Lathia JD et al (2015) Cancer stem cells in glioblastoma. Genes Dev 29(12):1203–1217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Parada LF, Dirks PB, Wechsler-Reya RJ (2017) Brain tumor stem cells remain in play. J Clin Oncol 35(21):2428–2431

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Schonberg DL et al (2014) Brain tumor stem cells: molecular characteristics and their impact on therapy. Mol Aspects Med 39:82–101

    Article  CAS  PubMed  Google Scholar 

  57. Calabrese C et al (2007) A perivascular niche for brain tumor stem cells. Cancer Cell 11(1):69–82

    Article  CAS  PubMed  Google Scholar 

  58. Silver DJ, Lathia JD (2018) Revealing the glioma cancer stem cell interactome, one niche at a time. J Pathol 244(3):260–264

    Article  PubMed  PubMed Central  Google Scholar 

  59. Holland EC (2000) Glioblastoma multiforme: the terminator. Proc Natl Acad Sci USA 97(12):6242–6244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Scherer HJ (1940) The forms of growth in gliomas and their practical significance. Brain 63(1):1–35

    Article  Google Scholar 

  61. Shiraki Y et al (2017) Significance of perivascular tumour cells defined by CD109 expression in progression of glioma. J Pathol 243(4):468–480

    Article  CAS  PubMed  Google Scholar 

  62. Wang X et al (2018) Reciprocal signaling between glioblastoma stem cells and differentiated tumor cells promotes malignant progression. Cell Stem Cell 22(4):514–528 e5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Bao S et al (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444(7120):756–760

    Article  CAS  PubMed  Google Scholar 

  64. Smith CL et al (2016) Migration phenotype of brain-cancer cells predicts patient outcomes. Cell Rep 15(12):2616–2624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Kaneko N et al (2010) New neurons clear the path of astrocytic processes for their rapid migration in the adult brain. Neuron 67(2):213–223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Brown JP et al (2003) Transient expression of doublecortin during adult neurogenesis. J Comp Neurol 467(1):1–10

    Article  CAS  PubMed  Google Scholar 

  67. Gleeson JG et al (1998) Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein. Cell 92(1):63–72

    Article  CAS  PubMed  Google Scholar 

  68. Moores CA et al (2004) Mechanism of microtubule stabilization by doublecortin. Mol Cell 14(6):833–839

    Article  CAS  PubMed  Google Scholar 

  69. Couillard-Despres S et al (2005) Doublecortin expression levels in adult brain reflect neurogenesis. Eur J Neurosci 21(1):1–14

    Article  PubMed  Google Scholar 

  70. Gleeson JG et al (1999) Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons. Neuron 23(2):257–271

    Article  CAS  PubMed  Google Scholar 

  71. Dobyns WB (2010) The clinical patterns and molecular genetics of lissencephaly and subcortical band heterotopia. Epilepsia 51(Suppl 1):5–9

    Article  PubMed  Google Scholar 

  72. Shahsavani M et al (2018) An in vitro model of lissencephaly: expanding the role of DCX during neurogenesis. Mol Psychiatry 23(7):1674

    Article  CAS  PubMed  Google Scholar 

  73. Filipovic R et al (2012) Increasing doublecortin expression promotes migration of human embryonic stem cell-derived neurons. Stem Cells 30(9):1852–1862

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Ocbina PJ et al (2006) Doublecortin is necessary for the migration of adult subventricular zone cells from neurospheres. Mol Cell Neurosci 33(2):126–135

    Article  CAS  PubMed  Google Scholar 

  75. Gdalyahu A et al (2004) DCX, a new mediator of the JNK pathway. EMBO J 23(4):823–832

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Jin J et al (2010) JNK phosphorylates Ser332 of doublecortin and regulates its function in neurite extension and neuronal migration. Dev Neurobiol 70(14):929–942

    Article  CAS  PubMed  Google Scholar 

  77. Schaar BT, Kinoshita K, McConnell SK (2004) Doublecortin microtubule affinity is regulated by a balance of kinase and phosphatase activity at the leading edge of migrating neurons. Neuron 41(2):203–213

    Article  CAS  PubMed  Google Scholar 

  78. Toriyama M et al (2012) Phosphorylation of doublecortin by protein kinase A orchestrates microtubule and actin dynamics to promote neuronal progenitor cell migration. J Biol Chem 287(16):12691–12702

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Daou MC et al (2005) Doublecortin is preferentially expressed in invasive human brain tumors. Acta Neuropathol 110(5):472–480

    Article  CAS  PubMed  Google Scholar 

  80. Masui K et al (2008) Evaluation of sensitivity and specificity of doublecortin immunostatining for the detection of infiltrating glioma cells. Brain Tumor Pathol 25(1):1–7

    Article  PubMed  Google Scholar 

  81. Santra M et al (2011) Effect of doublecortin on self-renewal and differentiation in brain tumor stem cells. Cancer Sci 102(7):1350–1357

    Article  CAS  PubMed  Google Scholar 

  82. Tapon N, Hall A (1997) Rho, Rac and Cdc42 GTPases regulate the organization of the actin cytoskeleton. Curr Opin Cell Biol 9(1):86–92

    Article  CAS  PubMed  Google Scholar 

  83. Khodosevich K, Monyer H (2010) Signaling involved in neurite outgrowth of postnatally born subventricular zone neurons in vitro. BMC Neurosci 11:18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Leong SY et al (2011) The Rho kinase pathway regulates mouse adult neural precursor cell migration. Stem Cells 29(2):332–343

    Article  CAS  PubMed  Google Scholar 

  85. Ballester-Lurbe B et al (2015) RhoE deficiency alters postnatal subventricular zone development and the number of calbindin-expressing neurons in the olfactory bulb of mouse. Brain Struct Funct 220(6):3113–3130

    Article  CAS  PubMed  Google Scholar 

  86. Ota H et al (2014) Speed control for neuronal migration in the postnatal brain by Gmip-mediated local inactivation of RhoA. Nat Commun 5:4532

    Article  CAS  PubMed  Google Scholar 

  87. Wong K et al (2001) Signal transduction in neuronal migration: roles of GTPase activating proteins and the small GTPase Cdc42 in the Slit-Robo pathway. Cell 107(2):209–221

    Article  CAS  PubMed  Google Scholar 

  88. Kwiatkowska A et al (2012) The small GTPase RhoG mediates glioblastoma cell invasion. Mol Cancer 11:65

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Danussi C et al (2013) RHPN2 drives mesenchymal transformation in malignant glioma by triggering RhoA activation. Cancer Res 73(16):5140–5150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Hirata E et al (2012) In vivo fluorescence resonance energy transfer imaging reveals differential activation of Rho-family GTPases in glioblastoma cell invasion. J Cell Sci 125(Pt 4):858–868

    Article  CAS  PubMed  Google Scholar 

  91. Fortin SP et al (2012) Cdc42 and the guanine nucleotide exchange factors Ect2 and trio mediate Fn14-induced migration and invasion of glioblastoma cells. Mol Cancer Res 10(7):958–968

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Franke TF et al (1995) The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase. Cell 81(5):727–736

    Article  CAS  PubMed  Google Scholar 

  93. Stambolic V et al (1998) Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell 95(1):29–39

    Article  CAS  PubMed  Google Scholar 

  94. Chen X et al (2015) Involvement of caspase-3/PTEN signaling pathway in isoflurane-induced decrease of self-renewal capacity of hippocampal neural precursor cells. Brain Res 1625:275–286

    Article  CAS  PubMed  Google Scholar 

  95. Groszer M et al (2001) Negative regulation of neural stem/progenitor cell proliferation by the Pten tumor suppressor gene in vivo. Science 294(5549):2186–2189

    Article  CAS  PubMed  Google Scholar 

  96. Ka M et al (2014) mTOR regulates brain morphogenesis by mediating GSK3 signaling. Development 141(21):4076–4086

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Peltier J, O’Neill A, Schaffer DV (2007) PI3K/Akt and CREB regulate adult neural hippocampal progenitor proliferation and differentiation. Dev Neurobiol 67(10):1348–1361

    Article  CAS  PubMed  Google Scholar 

  98. Zhang Q et al (2011) BDNF promotes EGF-induced proliferation and migration of human fetal neural stem/progenitor cells via the PI3K/Akt pathway. Molecules 16(12):10146–10156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Choi JK et al (2014) Granulocyte macrophage colony-stimulating factor shows anti-apoptotic activity via the PI3K-NF-kappaB-HIF-1alpha-survivin pathway in mouse neural progenitor cells. Mol Neurobiol 49(2):724–733

    Article  CAS  PubMed  Google Scholar 

  100. Li L et al (2002) PTEN in neural precursor cells: regulation of migration, apoptosis, and proliferation. Mol Cell Neurosci 20(1):21–29

    Article  CAS  PubMed  Google Scholar 

  101. Lachyankar MB et al (2000) A role for nuclear PTEN in neuronal differentiation. J Neurosci 20(4):1404–1413

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Li L et al (2008) Direct-current electrical field guides neuronal stem/progenitor cell migration. Stem Cells 26(8):2193–2200

    Article  CAS  PubMed  Google Scholar 

  103. Meng X et al (2011) PI3K mediated electrotaxis of embryonic and adult neural progenitor cells in the presence of growth factors. Exp Neurol 227(1):210–217

    Article  CAS  PubMed  Google Scholar 

  104. Katakowski M et al (2003) Phosphoinositide 3-kinase promotes adult subventricular neuroblast migration after stroke. J Neurosci Res 74(4):494–501

    Article  CAS  PubMed  Google Scholar 

  105. Kong X et al (2016) Tetramethylpyrazine promotes migration of neural precursor cells via activating the phosphatidylinositol 3-kinase pathway. Mol Neurobiol 53(9):6526–6539

    Article  CAS  PubMed  Google Scholar 

  106. Joy AM et al (2003) Migrating glioma cells activate the PI3-K pathway and display decreased susceptibility to apoptosis. J Cell Sci 116(Pt 21):4409–4417

    Article  CAS  PubMed  Google Scholar 

  107. Cantley LC, Neel BG (1999) New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc Natl Acad Sci USA 96(8):4240–4245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Gu JJ et al (2018) Suppression of microRNA-130b inhibits glioma cell proliferation and invasion, and induces apoptosis by PTEN/AKT signaling. Int J Mol Med 41(1):284–292

    CAS  PubMed  Google Scholar 

  109. Jaraiz-Rodriguez M et al (2017) A short region of Connexin43 reduces human glioma stem cell migration, invasion, and survival through Src, PTEN, and FAK. Stem Cell Reports 9(2):451–463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Pan S et al (2018) Decreased expression of ARHGAP15 promotes the development of colorectal cancer through PTEN/AKT/FOXO1 axis. Cell Death Dis 9(6):673

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Kuan CY et al (1999) The Jnk1 and Jnk2 protein kinases are required for regional specific apoptosis during early brain development. Neuron 22(4):667–676

    Article  CAS  PubMed  Google Scholar 

  112. Xu D et al (2014) Microcephaly-associated protein WDR62 regulates neurogenesis through JNK1 in the developing neocortex. Cell Rep 6(1):104–116

    Article  CAS  PubMed  Google Scholar 

  113. Hirai S et al (2006) The c-Jun N-terminal kinase activator dual leucine zipper kinase regulates axon growth and neuronal migration in the developing cerebral cortex. J Neurosci 26(46):11992–12002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Kawauchi T et al (2003) The in vivo roles of STEF/Tiam1, Rac1 and JNK in cortical neuronal migration. EMBO J 22(16):4190–4201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Wang X et al (2007) Targeted deletion of the mitogen-activated protein kinase kinase 4 gene in the nervous system causes severe brain developmental defects and premature death. Mol Cell Biol 27(22):7935–7946

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Yamasaki T et al (2011) Stress-activated protein kinase MKK7 regulates axon elongation in the developing cerebral cortex. J Neurosci 31(46):16872–16883

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Zhang F et al (2016) A Novel c-Jun N-terminal Kinase (JNK) signaling complex involved in neuronal migration during brain development. J Biol Chem 291(22):11466–11475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Westerlund N et al (2011) Phosphorylation of SCG10/stathmin-2 determines multipolar stage exit and neuronal migration rate. Nat Neurosci 14(3):305–313

    Article  CAS  PubMed  Google Scholar 

  119. Zhou X et al (2012) FRK controls migration and invasion of human glioma cells by regulating JNK/c-Jun signaling. J Neurooncol 110(1):9–19

    Article  CAS  PubMed  Google Scholar 

  120. Okada M et al (2014) JNK contributes to temozolomide resistance of stem-like glioblastoma cells via regulation of MGMT expression. Int J Oncol 44(2):591–599

    Article  CAS  PubMed  Google Scholar 

  121. Zhao HF et al (2016) PI3K p110beta isoform synergizes with JNK in the regulation of glioblastoma cell proliferation and migration through Akt and FAK inhibition. J Exp Clin Cancer Res 35:78

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Owens DF, Kriegstein AR (2002) Is there more to GABA than synaptic inhibition? Nat Rev Neurosci 3(9):715–727

    Article  CAS  PubMed  Google Scholar 

  123. Vidal Perez-Trevino GS (2011) NKCC1 cotransporters: keeping an ‘ion’ them. J Physiol 589(Pt 4):781–782

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Young SZ et al (2012) NKCC1 knockdown decreases neuron production through GABA(A)-regulated neural progenitor proliferation and delays dendrite development. J Neurosci 32(39):13630–13638

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Mejia-Gervacio S, Murray K, Lledo PM (2011) NKCC1 controls GABAergic signaling and neuroblast migration in the postnatal forebrain. Neural Dev 6:4

    Article  PubMed  PubMed Central  Google Scholar 

  126. Watkins S, Sontheimer H (2011) Hydrodynamic cellular volume changes enable glioma cell invasion. J Neurosci 31(47):17250–17259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Garzon-Muvdi T et al (2012) Regulation of brain tumor dispersal by NKCC1 through a novel role in focal adhesion regulation. PLoS Biol 10(5):e1001320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Haas BR et al (2011) With-No-Lysine Kinase 3 (WNK3) stimulates glioma invasion by regulating cell volume. Am J Physiol Cell Physiol 301(5):C1150–C1160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Schiapparelli P et al (2017) NKCC1 regulates migration ability of glioblastoma cells by modulation of actin dynamics and interacting with cofilin. EBioMedicine 21:94–103

    Article  PubMed  PubMed Central  Google Scholar 

  130. Kondapalli KC, Prasad H, Rao R (2014) An inside job: how endosomal Na(+)/H(+) exchangers link to autism and neurological disease. Front Cell Neurosci 8:172

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Kondapalli KC et al (2015) A leak pathway for luminal protons in endosomes drives oncogenic signalling in glioblastoma. Nat Commun 6:6289

    Article  CAS  PubMed  Google Scholar 

  132. Gomez Zubieta DM et al (2017) MicroRNA-135a regulates NHE9 to inhibit proliferation and migration of glioblastoma cells. Cell Commun Signal 15(1):55

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Smith DS, Greer PL, Tsai LH (2001) Cdk5 on the brain. Cell Growth Differ 12(6):277–283

    CAS  PubMed  Google Scholar 

  134. Ohshima T et al (1996) Targeted disruption of the cyclin-dependent kinase 5 gene results in abnormal corticogenesis, neuronal pathology and perinatal death. Proc Natl Acad Sci USA 93(20):11173–11178

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Chae T et al (1997) Mice lacking p35, a neuronal specific activator of Cdk5, display cortical lamination defects, seizures, and adult lethality. Neuron 18(1):29–42

    Article  CAS  PubMed  Google Scholar 

  136. Hirasawa M et al (2004) Perinatal abrogation of Cdk5 expression in brain results in neuronal migration defects. Proc Natl Acad Sci USA 101(16):6249–6254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Hirota Y et al (2007) Cyclin-dependent kinase 5 is required for control of neuroblast migration in the postnatal subventricular zone. J Neurosci 27(47):12829–12838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Yushan R et al (2015) Insights into the clinical value of cyclin-dependent kinase 5 in glioma: a retrospective study. World J Surg Oncol 13:223

    Article  PubMed  PubMed Central  Google Scholar 

  139. An JH et al (2009) Identification of gliotropic factors that induce human stem cell migration to malignant tumor. J Proteome Res 8(6):2873–2881

    Article  CAS  PubMed  Google Scholar 

  140. Klein R (2001) Excitatory Eph receptors and adhesive ephrin ligands. Curr Opin Cell Biol 13(2):196–203

    Article  CAS  PubMed  Google Scholar 

  141. Conover JC et al (2000) Disruption of Eph/ephrin signaling affects migration and proliferation in the adult subventricular zone. Nat Neurosci 3(11):1091–1097

    Article  CAS  PubMed  Google Scholar 

  142. Ricard J et al (2006) EphrinB3 regulates cell proliferation and survival in adult neurogenesis. Mol Cell Neurosci 31(4):713–722

    Article  CAS  PubMed  Google Scholar 

  143. Todd KL et al (2017) EphA4 regulates neuroblast and astrocyte organization in a neurogenic Niche. J Neurosci 37(12):3331–3341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Katakowski M et al (2005) EphB2 induces proliferation and promotes a neuronal fate in adult subventricular neural precursor cells. Neurosci Lett 385(3):204–209

    Article  CAS  PubMed  Google Scholar 

  145. Steinecke A et al (2014) EphA/ephrin A reverse signaling promotes the migration of cortical interneurons from the medial ganglionic eminence. Development 141(2):460–471

    Article  CAS  PubMed  Google Scholar 

  146. Nakada M et al (2010) The phosphorylation of ephrin-B2 ligand promotes glioma cell migration and invasion. Int J Cancer 126(5):1155–1165

    CAS  PubMed  PubMed Central  Google Scholar 

  147. Nakada M et al (2004) The phosphorylation of EphB2 receptor regulates migration and invasion of human glioma cells. Cancer Res 64(9):3179–3185

    Article  CAS  PubMed  Google Scholar 

  148. Nakada M et al (2006) Ephrin-B3 ligand promotes glioma invasion through activation of Rac1. Cancer Res 66(17):8492–8500

    Article  CAS  PubMed  Google Scholar 

  149. Sikkema AH et al (2012) EphB2 activity plays a pivotal role in pediatric medulloblastoma cell adhesion and invasion. Neuro Oncol 14(9):1125–1135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Krusche B et al (2016) EphrinB2 drives perivascular invasion and proliferation of glioblastoma stem-like cells. Elife 5:e14845

    Article  PubMed  PubMed Central  Google Scholar 

  151. Teng L et al (2013) Ligand-dependent EphB1 signaling suppresses glioma invasion and correlates with patient survival. Neuro Oncol 15(12):1710–1720

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Liu XS et al (2008) Functional response to SDF1 alpha through over-expression of CXCR152 on adult subventricular zone progenitor cells. Brain Res 1226:18–26

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Kokovay E et al (2010) Adult SVZ lineage cells home to and leave the vascular niche via differential responses to SDF1/CXCR153 signaling. Cell Stem Cell 7(2):163–173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Jin K et al (2003) Directed migration of neuronal precursors into the ischemic cerebral cortex and striatum. Mol Cell Neurosci 24(1):171–189

    Article  CAS  PubMed  Google Scholar 

  155. Salman H, Ghosh P, Kernie SG (2004) Subventricular zone neural stem cells remodel the brain following traumatic injury in adult mice. J Neurotrauma 21(3):283–292

    Article  PubMed  Google Scholar 

  156. Imitola J et al (2004) Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1α/CXC chemokine receptor 4 pathway. Proc Natl Acad Sci USA 101(52):18117–18122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Robin AM et al (2006) Stromal cell-derived factor 1alpha mediates neural progenitor cell motility after focal cerebral ischemia. J Cereb Blood Flow Metab 26(1):125–134

    Article  CAS  PubMed  Google Scholar 

  158. Itoh T et al (2009) The relationship between SDF-1alpha/CXCR158 and neural stem cells appearing in damaged area after traumatic brain injury in rats. Neurol Res 31(1):90–102

    Article  CAS  PubMed  Google Scholar 

  159. Mao W et al (2016) CXCL12/CXCR159 axis improves migration of neuroblasts along corpus callosum by stimulating MMP-2 secretion after traumatic brain injury in rats. Neurochem Res 41(6):1315–1322

    Article  CAS  PubMed  Google Scholar 

  160. Saha B et al (2013) Cortical lesion stimulates adult subventricular zone neural progenitor cell proliferation and migration to the site of injury. Stem Cell Res 11(3):965–977

    Article  PubMed  Google Scholar 

  161. Zhu M et al (2015) Human cerebrospinal fluid regulates proliferation and migration of stem cells through insulin-like growth factor-1. Stem Cells Dev 24(2):160–171

    Article  CAS  PubMed  Google Scholar 

  162. do Carmo A et al (2010) CXCL12/CXCR1 promotes motility and proliferation of glioma cells. Cancer Biol Ther 9(1):56–65

    Article  CAS  PubMed  Google Scholar 

  163. Gatti M et al (2013) Inhibition of CXCL12/CXCR163 autocrine/paracrine loop reduces viability of human glioblastoma stem-like cells affecting self-renewal activity. Toxicology 314(2–3):209–220

    Article  CAS  PubMed  Google Scholar 

  164. Wang S et al (2014) CXCL12-induced upregulation of FOXM1 expression promotes human glioblastoma cell invasion. Biochem Biophys Res Commun 447(1):1–6

    Article  CAS  PubMed  Google Scholar 

  165. Goffart N et al (2015) Adult mouse subventricular zones stimulate glioblastoma stem cells specific invasion through CXCL12/CXCR165 signaling. Neuro Oncol 17(1):81–94

    Article  CAS  PubMed  Google Scholar 

  166. Gravina GL et al (2017) The novel CXCR166 antagonist, PRX177561, reduces tumor cell proliferation and accelerates cancer stem cell differentiation in glioblastoma preclinical models. Tumour Biol 39(6):1010428317695528

    Article  PubMed  Google Scholar 

  167. Andrews WD, Barber M, Parnavelas JG (2007) Slit-Robo interactions during cortical development. J Anat 211(2):188–198

    Article  PubMed  PubMed Central  Google Scholar 

  168. Wu W et al (1999) Directional guidance of neuronal migration in the olfactory system by the protein Slit. Nature 400(6742):331–336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Nguyen-Ba-Charvet KT et al (2004) Multiple roles for slits in the control of cell migration in the rostral migratory stream. J Neurosci 24(6):1497–1506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Guerrero-Cazares H et al (2017) Brief report: Robo1 regulates the migration of human subventricular zone neural progenitor cells during development. Stem Cells 35(7):1860–1865

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Dallol A et al (2003) Frequent epigenetic inactivation of the SLIT2 gene in gliomas. Oncogene 22(29):4611–4616

    Article  CAS  PubMed  Google Scholar 

  172. Astuti D et al (2004) SLIT2 promoter methylation analysis in neuroblastoma, Wilms’ tumour and renal cell carcinoma. Br J Cancer 90(2):515–521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Yiin JJ et al (2009) Slit2 inhibits glioma cell invasion in the brain by suppression of Cdc42 activity. Neuro Oncol 11(6):779–789

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Mertsch S et al (2008) Slit2 involvement in glioma cell migration is mediated by Robo1 receptor. J Neurooncol 87(1):1–7

    Article  CAS  PubMed  Google Scholar 

  175. Xu Y et al (2010) Slit2/Robo1 signaling in glioma migration and invasion. Neurosci Bull 26(6):474–478

    Article  PubMed  PubMed Central  Google Scholar 

  176. Casazza A, Fazzari P, Tamagnone L (2007) Semaphorin signals in cell adhesion and cell migration: functional role and molecular mechanisms. Adv Exp Med Biol 600:90–108

    Article  PubMed  Google Scholar 

  177. Melendez-Herrera E et al (2008) Semaphorin-3A and its receptor neuropilin-1 are predominantly expressed in endothelial cells along the rostral migratory stream of young and adult mice. Cell Tissue Res 333(2):175–184

    Article  CAS  PubMed  Google Scholar 

  178. Kong Y et al (2016) Structural basis for Plexin activation and regulation. Neuron 91(3):548–560

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Falk J et al (2005) Dual functional activity of semaphorin 3B is required for positioning the anterior commissure. Neuron 48(1):63–75

    Article  PubMed  Google Scholar 

  180. Tamamaki N et al (2003) Evidence that Sema3A and Sema3F regulate the migration of GABAergic neurons in the developing neocortex. J Comp Neurol 455(2):238–248

    Article  CAS  PubMed  Google Scholar 

  181. Andrews WD et al (2016) Altered proliferative ability of neuronal progenitors in PlexinA1 mutant mice. J Comp Neurol 524(3):518–534

    Article  CAS  PubMed  Google Scholar 

  182. Hirschberg A et al (2010) Gene deletion mutants reveal a role for semaphorin receptors of the plexin-B family in mechanisms underlying corticogenesis. Mol Cell Biol 30(3):764–780

    Article  CAS  PubMed  Google Scholar 

  183. Sun T, Li W, Ling S (2016) miR-30c and semaphorin 3A determine adult neurogenesis by regulating proliferation and differentiation of stem cells in the subventricular zones of mouse. Cell Prolif 49(3):270–280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Saha B et al (2012) Plexin-B2 regulates the proliferation and migration of neuroblasts in the postnatal and adult subventricular zone. J Neurosci 32(47):16892–16905

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Man J et al (2014) Sema3C promotes the survival and tumorigenicity of glioma stem cells through Rac1 activation. Cell Rep 9(5):1812–1826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Bagci T et al (2009) Autocrine semaphorin 3A signaling promotes glioblastoma dispersal. Oncogene 28(40):3537–3550

    Article  CAS  PubMed  Google Scholar 

  187. Zhou X et al (2012) Effects of SEMA3G on migration and invasion of glioma cells. Oncol Rep 28(1):269–275

    CAS  PubMed  Google Scholar 

  188. Behar TN et al (1997) Neurotrophins stimulate chemotaxis of embryonic cortical neurons. Eur J Neurosci 9(12):2561–2570

    Article  CAS  PubMed  Google Scholar 

  189. Ohmiya M et al (2001) Administration of FGF-2 to embryonic mouse brain induces hydrocephalic brain morphology and aberrant differentiation of neurons in the postnatal cerebral cortex. J Neurosci Res 65(3):228–235

    Article  CAS  PubMed  Google Scholar 

  190. Fukumitsu H et al (2006) Brain-derived neurotrophic factor participates in determination of neuronal laminar fate in the developing mouse cerebral cortex. J Neurosci 26(51):13218–13230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Chiaramello S et al (2007) BDNF/TrkB interaction regulates migration of SVZ precursor cells via PI3-K and MAP-K signalling pathways. Eur J Neurosci 26(7):1780–1790

    Article  CAS  PubMed  Google Scholar 

  192. Petridis AK, El Maarouf A (2011) Brain-derived neurotrophic factor levels influence the balance of migration and differentiation of subventricular zone cells, but not guidance to the olfactory bulb. J Clin Neurosci 18(2):265–270

    Article  CAS  PubMed  Google Scholar 

  193. Xiong J et al (2015) Mature brain-derived neurotrophic factor and its receptor TrkB are upregulated in human glioma tissues. Oncol Lett 10(1):223–227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Johnston AL et al (2007) The p75 neurotrophin receptor is a central regulator of glioma invasion. PLoS Biol 5(8):e212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  195. Xiong J et al (2013) Mature BDNF promotes the growth of glioma cells in vitro. Oncol Rep 30(6):2719–2724

    Article  CAS  PubMed  Google Scholar 

  196. Lawn S et al (2015) Neurotrophin signaling via TrkB and TrkC receptors promotes the growth of brain tumor-initiating cells. J Biol Chem 290(6):3814–3824

    Article  CAS  PubMed  Google Scholar 

  197. Li YS et al (1990) Cloning and expression of a developmentally regulated protein that induces mitogenic and neurite outgrowth activity. Science 250(4988):1690–1694

    Article  CAS  PubMed  Google Scholar 

  198. Rauvala H, Pihlaskari R (1987) Isolation and some characteristics of an adhesive factor of brain that enhances neurite outgrowth in central neurons. J Biol Chem 262(34):16625–16635

    CAS  PubMed  Google Scholar 

  199. Maeda N, Noda M (1998) Involvement of receptor-like protein tyrosine phosphatase zeta/RPTPbeta and its ligand pleiotrophin/heparin-binding growth-associated molecule (HB-GAM) in neuronal migration. J Cell Biol 142(1):203–216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  200. Qin EY et al (2017) Neural precursor-derived pleiotrophin mediates subventricular zone invasion by glioma. Cell 170(5):845–859.e19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  201. Zhang L et al (2004) Overexpression of heparin-binding growth-associated molecule in malignant glioma cells. Neurol Med Chir (Tokyo) 44(12):637–643 discussion 644–5

    Article  Google Scholar 

  202. Mentlein R, Held-Feindt J (2002) Pleiotrophin, an angiogenic and mitogenic growth factor, is expressed in human gliomas. J Neurochem 83(4):747–753

    Article  CAS  PubMed  Google Scholar 

  203. Ma J et al (2014) Co-expression of midkine and pleiotrophin predicts poor survival in human glioma. J Clin Neurosci 21(11):1885–1890

    Article  CAS  PubMed  Google Scholar 

  204. Zhang L et al (2015) Pleiotrophin promotes vascular abnormalization in gliomas and correlates with poor survival in patients with astrocytomas. Sci Signal 8(406):ra125

    Article  CAS  PubMed  Google Scholar 

  205. Koyama-Nasu R et al (2014) The pleiotrophin-ALK axis is required for tumorigenicity of glioblastoma stem cells. Oncogene 33(17):2236–2244

    Article  CAS  PubMed  Google Scholar 

  206. Powers C et al (2002) Pleiotrophin signaling through anaplastic lymphoma kinase is rate-limiting for glioblastoma growth. J Biol Chem 277(16):14153–14158

    Article  CAS  PubMed  Google Scholar 

  207. Ulbricht U et al (2003) Expression and function of the receptor protein tyrosine phosphatase zeta and its ligand pleiotrophin in human astrocytomas. J Neuropathol Exp Neurol 62(12):1265–1275

    Article  CAS  PubMed  Google Scholar 

  208. Hynes RO (2002) Integrins: bidirectional, allosteric signaling machines. Cell 110(6):673–687

    Article  CAS  PubMed  Google Scholar 

  209. Belvindrah R et al (2007) Beta1 integrins control the formation of cell chains in the adult rostral migratory stream. J Neurosci 27(10):2704–2717

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  210. Jacques TS et al (1998) Neural precursor cell chain migration and division are regulated through different beta1 integrins. Development 125(16):3167–3177

    CAS  PubMed  Google Scholar 

  211. Flanagan LA et al (2006) Regulation of human neural precursor cells by laminin and integrins. J Neurosci Res 83(5):845–856

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  212. Alfonso J et al (2015) Downregulation of sphingosine 1-phosphate receptor 1 promotes the switch from tangential to radial migration in the OB. J Neurosci 35(40):13659–13672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  213. Lathia JD et al (2010) Integrin alpha 6 regulates glioblastoma stem cells. Cell Stem Cell 6(5):421–432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  214. Ying M et al (2014) Kruppel-like factor-9 (KLF9) inhibits glioblastoma stemness through global transcription repression and integrin alpha6 inhibition. J Biol Chem 289(47):32742–32756

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  215. Blandin AF et al (2016) Glioma cell dispersion is driven by alpha5 integrin-mediated cell-matrix and cell-cell interactions. Cancer Lett 376(2):328–338

    Article  CAS  PubMed  Google Scholar 

  216. Haas TL et al (2017) Integrin alpha7 is a functional marker and potential therapeutic target in glioblastoma. Cell Stem Cell 21(1):35–50 e9

    Article  CAS  PubMed  Google Scholar 

  217. Tilghman J et al (2016) Regulation of glioblastoma tumor-propagating cells by the integrin partner tetraspanin CD151. Neoplasia 18(3):185–198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  218. Zhou P et al (2015) CD151-alpha3beta1 integrin complexes are prognostic markers of glioblastoma and cooperate with EGFR to drive tumor cell motility and invasion. Oncotarget 6(30):29675–29693

    Article  PubMed  PubMed Central  Google Scholar 

  219. Liu Z et al (2016) EGFRvIII/integrin beta3 interaction in hypoxic and vitronectinenriching microenvironment promote GBM progression and metastasis. Oncotarget 7(4):4680–4694

    PubMed  Google Scholar 

  220. Harris TJ, Tepass U (2010) Adherens junctions: from molecules to morphogenesis. Nat Rev Mol Cell Biol 11(7):502–514

    Article  CAS  PubMed  Google Scholar 

  221. Porlan E et al (2014) MT5-MMP regulates adult neural stem cell functional quiescence through the cleavage of N-cadherin. Nat Cell Biol 16(7):629–638

    Article  CAS  PubMed  Google Scholar 

  222. Yagita Y et al (2009) N-cadherin mediates interaction between precursor cells in the subventricular zone and regulates further differentiation. J Neurosci Res 87(15):3331–3342

    Article  CAS  PubMed  Google Scholar 

  223. Fujikake K et al (2018) Detachment of chain-forming neuroblasts by Fyn-mediated control of cell–cell adhesion in the postnatal brain. J Neurosci 38(19):4598–4609

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  224. Klingener M et al (2014) N-cadherin promotes recruitment and migration of neural progenitor cells from the SVZ neural stem cell niche into demyelinated lesions. J Neurosci 34(29):9590–9606

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  225. Cao L et al (2015) Physiological electrical signals promote chain migration of neuroblasts by up-regulating P2Y1 purinergic receptors and enhancing cell adhesion. Stem Cell Rev 11(1):75–86

    Article  CAS  Google Scholar 

  226. Kim MY et al (2010) Bone morphogenetic protein 4 stimulates attachment of neurospheres and astrogenesis of neural stem cells in neurospheres via phosphatidylinositol 3 kinase-mediated upregulation of N-cadherin. Neuroscience 170(1):8–15

    Article  CAS  PubMed  Google Scholar 

  227. Chen D et al (2015) E-cadherin maintains the activity of neural stem cells and inhibits the migration. Int J Clin Exp Pathol 8(11):14247–14251

    CAS  PubMed  PubMed Central  Google Scholar 

  228. Schulte JD et al (2013) Cadherin-11 regulates motility in normal cortical neural precursors and glioblastoma. PLoS One 8(8):e70962

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  229. Thiery JP, Sleeman JP (2006) Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol 7(2):131–142

    Article  CAS  PubMed  Google Scholar 

  230. Utsuki S et al (2002) Relationship between the expression of E-, N-cadherins and beta-catenin and tumor grade in astrocytomas. J Neurooncol 57(3):187–192

    Article  PubMed  Google Scholar 

  231. Noh MG et al (2017) Prognostic significance of E-cadherin and N-cadherin expression in Gliomas. BMC Cancer 17(1):583

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  232. Kaur H et al (2012) Cadherin-11, a marker of the mesenchymal phenotype, regulates glioblastoma cell migration and survival in vivo. Mol Cancer Res 10(3):293–304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  233. Rutishauser U et al (1988) The neural cell adhesion molecule (NCAM) as a regulator of cell-cell interactions. Science 240(4848):53–57

    Article  CAS  PubMed  Google Scholar 

  234. Cunningham BA et al (1987) Neural cell adhesion molecule: structure, immunoglobulin-like domains, cell surface modulation, and alternative RNA splicing. Science 236(4803):799–806

    Article  CAS  PubMed  Google Scholar 

  235. Seki T, Arai Y (1993) Highly polysialylated neural cell adhesion molecule (NCAM-H) is expressed by newly generated granule cells in the dentate gyrus of the adult rat. J Neurosci 13(6):2351–2358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  236. Finne J et al (1983) Occurrence of alpha 2-8 linked polysialosyl units in a neural cell adhesion molecule. Biochem Biophys Res Commun 112(2):482–487

    Article  CAS  PubMed  Google Scholar 

  237. Doetsch F, Alvarez-Buylla A (1996) Network of tangential pathways for neuronal migration in adult mammalian brain. Proc Natl Acad Sci USA 93(25):14895–14900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  238. Tomasiewicz H et al (1993) Genetic deletion of a neural cell adhesion molecule variant (N-CAM-180) produces distinct defects in the central nervous system. Neuron 11(6):1163–1174

    Article  CAS  PubMed  Google Scholar 

  239. Cremer H et al (1994) Inactivation of the N-CAM gene in mice results in size reduction of the olfactory bulb and deficits in spatial learning. Nature 367(6462):455–459

    Article  CAS  PubMed  Google Scholar 

  240. Ono K et al (1994) N-CAM mutation inhibits tangential neuronal migration and is phenocopied by enzymatic removal of polysialic acid. Neuron 13(3):595–609

    Article  CAS  PubMed  Google Scholar 

  241. Hu H et al (1996) The role of polysialic acid in migration of olfactory bulb interneuron precursors in the subventricular zone. Neuron 16(4):735–743

    Article  CAS  PubMed  Google Scholar 

  242. Rockle I, Hildebrandt H (2016) Deficits of olfactory interneurons in polysialyltransferase- and NCAM-deficient mice. Dev Neurobiol 76(4):421–433

    Article  CAS  PubMed  Google Scholar 

  243. Battista D, Rutishauser U (2010) Removal of polysialic acid triggers dispersion of subventricularly derived neuroblasts into surrounding CNS tissues. J Neurosci 30(11):3995–4003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  244. Figarella-Branger DF, Durbec PL, Rougon GN (1990) Differential spectrum of expression of neural cell adhesion molecule isoforms and L1 adhesion molecules on human neuroectodermal tumors. Cancer Res 50(19):6364–6370

    CAS  PubMed  Google Scholar 

  245. Figarella-Branger D et al (1992) Expression of adhesion molecules N. CAM, L1 and HNK1 epitope by medulloblastoma. Rev Neurol Paris 148(6–7):417–422

    CAS  PubMed  Google Scholar 

  246. Petridis AK et al (2009) Polysialic acid overexpression in malignant astrocytomas. Acta Neurochir (Wien) 151(6):601–603 (discussion 603-4)

    Article  Google Scholar 

  247. Suzuki M et al (2005) Polysialic acid facilitates tumor invasion by glioma cells. Glycobiology 15(9):887–894

    Article  CAS  PubMed  Google Scholar 

  248. Page-McCaw A, Ewald AJ, Werb Z (2007) Matrix metalloproteinases and the regulation of tissue remodelling. Nat Rev Mol Cell Biol 8(3):221–233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  249. Kang SS et al (2008) Inhibition of matrix metalloproteinase-9 attenuated neural progenitor cell migration after photothrombotic ischemia. Brain Res 1228:20–26

    Article  CAS  PubMed  Google Scholar 

  250. Lee SR et al (2006) Involvement of matrix metalloproteinase in neuroblast cell migration from the subventricular zone after stroke. J Neurosci 26(13):3491–3495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  251. Kanemitsu M et al (2017) EMMPRIN overexpression in SVZ neural progenitor cells increases their migration towards ischemic cortex. Exp Neurol 297:14–24

    Article  CAS  PubMed  Google Scholar 

  252. Bovetti S et al (2007) Subventricular zone-derived neuroblast migration to the olfactory bulb is modulated by matrix remodelling. Eur J Neurosci 25(7):2021–2033

    Article  PubMed  Google Scholar 

  253. Lin KT et al (2008) Ephrin-B2-induced cleavage of EphB2 receptor is mediated by matrix metalloproteinases to trigger cell repulsion. J Biol Chem 283(43):28969–28979

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  254. Forsyth PA et al (1999) Gelatinase-A (MMP-2), gelatinase-B (MMP-9) and membrane type matrix metalloproteinase-1 (MT1-MMP) are involved in different aspects of the pathophysiology of malignant gliomas. Br J Cancer 79(11–12):1828–1835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  255. Nan Y et al (2010) MiRNA-451 plays a role as tumor suppressor in human glioma cells. Brain Res 1359:14–21

    Article  CAS  PubMed  Google Scholar 

  256. Sun L et al (2011) MicroRNA-10b induces glioma cell invasion by modulating MMP-14 and uPAR expression via HOXD10. Brain Res 1389:9–18

    Article  CAS  PubMed  Google Scholar 

  257. Zheng X et al (2013) MiR-15b and miR-152 reduce glioma cell invasion and angiogenesis via NRP-2 and MMP-3. Cancer Lett 329(2):146–154

    Article  CAS  PubMed  Google Scholar 

  258. Lakka SS et al (2004) Inhibition of cathepsin B and MMP-9 gene expression in glioblastoma cell line via RNA interference reduces tumor cell invasion, tumor growth and angiogenesis. Oncogene 23(27):4681–4689

    Article  CAS  PubMed  Google Scholar 

  259. Inoue A et al (2010) Cancer stem-like cells of glioblastoma characteristically express MMP-13 and display highly invasive activity. Int J Oncol 37(5):1121–1131

    CAS  PubMed  Google Scholar 

  260. Lathia JD et al (2011) Direct in vivo evidence for tumor propagation by glioblastoma cancer stem cells. PLoS One 6(9):e24807

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  261. Vakoc BJ et al (2009) Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging. Nat Med 15(10):1219–1223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  262. Guerrero-Cazares H, Chaichana KL, Quinones-Hinojosa A (2009) Neurosphere culture and human organotypic model to evaluate brain tumor stem cells. Methods Mol Biol 568:73–83

    Article  PubMed  PubMed Central  Google Scholar 

  263. Ohnishi T et al (1998) A novel model of glioma cell invasion using organotypic brain slice culture. Cancer Res 58(14):2935–2940

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Authors are funded by the NCI (R21CA199295, R01CA183827, R01CA195503, R01CA216855, R01CA200399, R43CA221490), NINDS (R03NS109444), Florida State Department of Health Research Grant, and the Mayo Clinic Graduate School. AQH is supported by the William J. and Charles H. Mayo Professorship and the Mayo Clinic Clinician Investigator.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hugo Guerrero-Cázares.

Ethics declarations

Conflict of interest

The authors declare there is no conflict of interest regarding the publication of this article.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zarco, N., Norton, E., Quiñones-Hinojosa, A. et al. Overlapping migratory mechanisms between neural progenitor cells and brain tumor stem cells. Cell. Mol. Life Sci. 76, 3553–3570 (2019). https://doi.org/10.1007/s00018-019-03149-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-019-03149-7

Keywords

Navigation