nach oben

Erschienen in:

21.02.2018 | Laboratory Investigation

The expression of the MSC-marker CD73 and of NF2/Merlin are correlated in meningiomas

verfasst von: Elmar Kirches, Tabea Steffen, Natalie Waldt, Eva Hebert, Doreen Pachow, Annette Wilisch-Neumann, Gerburg Keilhoff, Thomas Schneider, Werner E. K. Braunsdorf, Jan-Peter Warnke, Christian Mawrin

Erschienen in: Journal of Neuro-Oncology | Ausgabe 2/2018

Einloggen, um Zugang zu erhalten

Abstract

Mesenchymal stem cells (MSC) have been found in various cancers and were discussed to influence tumor biology. Cells fulfilling the complete MSC criteria, including surface marker expression (CD73, CD90, CD105) and tri-lineage differentiation, have been isolated solely from a low percentage of high-grade meningiomas. In contrast, pure co-expression of the surface-markers was relatively frequent, raising the question for an additional role of these membrane proteins in meningiomas. Therefore, here we analyzed the expression of CD73, CD90 and CD105 in a series of meningiomas of all grades. Although no significant association of any marker with meningeal tumor growth per se or with tumor-grade was observed, we detected a positive Pearson correlation (r = 0.55, p ≤ 0.05) in low-grade tumors between CD73 and the most relevant tumor suppressor NF2/Merlin, supported by a tendency of lower CD73 expression in cases with allelic losses at the NF2-locus, which express significantly lower NF2/Merlin-mRNA (p ≤ 0.05). In two pairs of syngenous meningeal or meningioma cell lines with or without shRNA-mediated knockdown of NF2/Merlin a nearly complete loss of CD73 mRNA expression was observed after the knockdown (p ≤ 0.001). This suggested that the correlation observed in tumors may result from a direct functional link between Merlin and CD73. Since CD73 is a 5′-exonucleotidase (termed NT5E), we discuss a potential role of NT5E-mediated purinergic signaling to modulate actin-cytoskeleton and cell contacts, which may be a functional link to NF2/Merlin.

Nur mit Berechtigung zugänglich

Mawrin C, Perry A (2010) Pathological classification and molecular genetics of meningiomas. J Neurooncol 99:379–391CrossRefPubMed

Perry A, Scheithauer BW, Stafford SL, Lohse CM, Wollan PC (1999) “Malignancy” in meningiomas: a clinicopathologic study of 116 patients, with grading implications. Cancer 85:2046–2056PubMed

Mawrin C, Chung C, Preusser M (2015) Biology and clinical management challenges in meningioma. American Society of Clinical Oncology educational book/ASCO American Society of Clinical Oncology Meeting, pp e106–e115. https://doi.org/10.14694/EdBook_AM.2015.35.e106

Weber RG, Bostrom J, Wolter M, Baudis M, Collins VP, Reifenberger G, Lichter P (1997) Analysis of genomic alterations in benign, atypical, and anaplastic meningiomas: toward a genetic model of meningioma progression. Proc Natl Acad Sci USA 94:14719–14724CrossRefPubMedPubMedCentral

Ruttledge MH, Sarrazin J, Rangaratnam S, Phelan CM, Twist E, Merel P, Delattre O, Thomas G, Nordenskjold M, Collins VP et al (1994) Evidence for the complete inactivation of the NF2 gene in the majority of sporadic meningiomas. Nat Genet 6:180–184CrossRefPubMed

Ruttledge MH, Xie YG, Han FY, Peyrard M, Collins VP, Nordenskjold M, Dumanski JP (1994) Deletions on chromosome 22 in sporadic meningioma. Genes Chromosom Cancer 10:122–130CrossRefPubMed

Kalamarides M, Stemmer-Rachamimov AO, Niwa-Kawakita M, Chareyre F, Taranchon E, Han ZY, Martinelli C, Lusis EA, Hegedus B, Gutmann DH, Giovannini M (2011) Identification of a progenitor cell of origin capable of generating diverse meningioma histological subtypes. Oncogene 30:2333–2344CrossRefPubMed

Rhee K-J, Lee JI, Eom YW (2015) Mesenchymal stem cell-mediated effects of tumor support or suppression. Int J Mol Sci 16:30015–30033. https://doi.org/10.3390/ijms161226215 CrossRefPubMedPubMedCentral

Norozi F, Ahmadzadeh A, Shahrabi S, Vosoughi T, Saki N (2016) Mesenchymal stem cells as a double-edged sword in suppression or progression of solid tumor cells. Tumor Biol 37:11679–11689. https://doi.org/10.1007/s13277-016-5187-7 CrossRef

10.

Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW, Richardson AL, Polyak K, Tubo R, Weinberg RA (2007) Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 449:557–563. https://doi.org/10.1038/nature06188 CrossRefPubMed

11.

Shinagawa K, Kitadai Y, Tanaka M, Sumida T, Kodama M, Higashi Y, Tanaka S, Yasui W, Chayama K (2010) Mesenchymal stem cells enhance growth and metastasis of colon cancer. Int J Cancer 127:2323–2333. https://doi.org/10.1002/ijc.25440 CrossRefPubMed

12.

Tsukamoto S, Honoki K, Fujii H, Tohma Y, Kido A, Mori T, Tsujiuchi T, Tanaka Y (2012) Mesenchymal stem cells promote tumor engraftment and metastatic colonization in rat osteosarcoma model. Int J Oncol 40:163–169. https://doi.org/10.3892/ijo.2011.1220 PubMed

13.

Comsa S, Ciuculescu F, Raica M (2012) Mesenchymal stem cell-tumor cell cooperation in breast cancer vasculogenesis. Molecular medicine reports 5:1175–1180. https://doi.org/10.3892/mmr.2012.796 PubMed

14.

Weber CE, Kothari AN, Wai PY, Li NY, Driver J, Zapf MA, Franzen CA, Gupta GN, Osipo C, Zlobin A, Syn WK, Zhang J, Kuo PC, Mi Z (2015) Osteopontin mediates an MZF1-TGF-beta1-dependent transformation of mesenchymal stem cells into cancer-associated fibroblasts in breast cancer. Oncogene 34:4821–4833. https://doi.org/10.1038/onc.2014.410 CrossRefPubMed

15.

Coffman LG, Choi YJ, McLean K, Allen BL, di Magliano MP, Buckanovich RJ (2016) Human carcinoma-associated mesenchymal stem cells promote ovarian cancer chemotherapy resistance via a BMP4/HH signaling loop. Oncotarget 7:6916–6932. https://doi.org/10.18632/oncotarget.6870 CrossRefPubMedPubMedCentral

16.

Hu D, Wang X, Mao Y, Zhou L (2012) Identification of CD105 (endoglin)-positive stem-like cells in rhabdoid meningioma. J Neurooncol 106:505–517CrossRefPubMed

17.

Lim HY, Kim KM, Kim BK, Shim JK, Lee JH, Huh YM, Kim SH, Kim EH, Park EK, Shim KW, Chang JH, Kim DS, Kim SH, Hong YK, Lee SJ, Kang SG (2013) Isolation of mesenchymal stem-like cells in meningioma specimens. Int J Oncol 43:1260–1268. https://doi.org/10.3892/ijo.2013.2053 CrossRefPubMed

18.

Duff SE, Li C, Garland JM, Kumar S (2003) CD105 is important for angiogenesis: evidence and potential applications. FASEB J 17:984–992. https://doi.org/10.1096/fj.02-0634rev CrossRefPubMed

19.

Dallas NA, Samuel S, Xia L, Fan F, Gray MJ, Lim SJ, Ellis LM (2008) Endoglin (CD105): a marker of tumor vasculature and potential target for therapy. Clin Cancer Res 14:1931–1937. https://doi.org/10.1158/1078-0432.ccr-07-4478 CrossRefPubMed

20.

Barresi V, Cerasoli S, Vitarelli E, Tuccari G (2007) Density of microvessels positive for CD105 (endoglin) is related to prognosis in meningiomas. Acta Neuropathol 114:147–156. https://doi.org/10.1007/s00401-007-0251-4 CrossRefPubMed

21.

Barresi V, Cerasoli S, Tuccari G (2008) Correlative evidence that tumor cell-derived caveolin-1 mediates angiogenesis in meningiomas. Neuropathology 28:472–478. https://doi.org/10.1111/j.1440-1789.2008.00902.x CrossRefPubMed

22.

Barresi V, Alafaci C, Salpietro F, Tuccari G (2008) Sstr2A immunohistochemical expression in human meningiomas: is there a correlation with the histological grade, proliferation or microvessel density? Oncol Rep 20:485–492PubMed

23.

Ling C, Pouget C, Rech F, Pflaum R, Treffel M, Bielle F, Mokhtari K, Casse JM, Vignaud JM, Kalamarides M, Peyre M, Gauchotte G (2016) Endothelial cell hypertrophy and microvascular proliferation in meningiomas are correlated with higher histological grade and shorter progression-free survival. J Neuropathol Exp Neurol 75:1160–1170. https://doi.org/10.1093/jnen/nlw095 CrossRefPubMed

24.

Inoue A, Tanaka J, Takahashi H, Kohno S, Ohue S, Umakoshi A, Gotoh K, Ohnishi T (2016) Blood vessels expressing CD90 in human and rat brain tumors. Neuropathology 36:168–180. https://doi.org/10.1111/neup.12244 CrossRefPubMed

25.

Di Virgilio F, Adinolfi E (2017) Extracellular purines, purinergic receptors and tumor growth. Oncogene 36:293–303. https://doi.org/10.1038/onc.2016.206 CrossRefPubMed

26.

Mawrin C, Wolke C, Haase D, Kruger S, Firsching R, Keilhoff G, Paulus W, Gutmann DH, Lal A, Lendeckel U (2010) Reduced activity of cd13/aminopeptidase n (APN) in aggressive meningiomas is associated with increased levels of SPARC. Brain Pathol 20:200–210CrossRefPubMed

27.

Pachow D, Andrae N, Kliese N, Angenstein F, Stork O, Wilisch-Neumann A, Kirches E, Mawrin C (2013) mTORC1 inhibitors suppress meningioma growth in mouse models. Clin Cancer Res 19:1180–1189CrossRefPubMed

28.

Puttmann S, Senner V, Braune S, Hillmann B, Exeler R, Rickert CH, Paulus W (2005) Establishment of a benign meningioma cell line by hTERT-mediated immortalization. Lab Invest 85:1163–1171CrossRefPubMed

29.

Striedinger K, Vandenberg SR, Baia GS, McDermott MW, Gutmann DH, Lal A (2008) The neurofibromatosis 2 tumor suppressor gene product, merlin, regulates human meningioma cell growth by signaling through YAP. Neoplasia 10:1204–1212CrossRefPubMedPubMedCentral

30.

Amin ND, Bai G, Klug JR, Bonanomi D, Pankratz MT, Gifford WD, Hinckley CA, Sternfeld MJ, Driscoll SP, Dominguez B, Lee K-F, Jin X, Pfaff SL (2015) Loss of motoneuron-specific microRNA-218 causes systemic neuromuscular failure. Science 350:1525–1529. https://doi.org/10.1126/science.aad2509 CrossRefPubMedPubMedCentral

31.

Allard B, Beavis PA, Darcy PK, Stagg J (2016) Immunosuppressive activities of adenosine in cancer. Curr Opin Pharmacol 29:7–16. https://doi.org/10.1016/j.coph.2016.04.001 CrossRefPubMed

32.

Young A, Ngiow SF, Barkauskas DS, Sult E, Hay C, Blake SJ, Huang Q, Liu J, Takeda K, Teng MW, Sachsenmeier K, Smyth MJ (2016) Co-inhibition of CD73 and A2AR adenosine signaling improves anti-tumor immune responses. Cancer Cell 30:391–403. https://doi.org/10.1016/j.ccell.2016.06.025 CrossRefPubMed

33.

Wang L, Tang S, Wang Y, Xu S, Yu J, Zhi X, Ou Z, Yang J, Zhou P, Shao Z (2013) Ecto-5′-nucleotidase (CD73) promotes tumor angiogenesis. Clin Exp Metastas 30:671–680. https://doi.org/10.1007/s10585-013-9571-z CrossRef

34.

Turcotte M, Spring K, Pommey S, Chouinard G, Cousineau I, George J, Chen GM, Gendoo DM, Haibe-Kains B, Karn T, Rahimi K, Le Page C, Provencher D, Mes-Masson AM, Stagg J (2015) CD73 is associated with poor prognosis in high-grade serous ovarian cancer. Cancer Res 75:4494–4503. https://doi.org/10.1158/0008-5472.can-14-3569 CrossRefPubMed

35.

Loi S, Pommey S, Haibe-Kains B, Beavis PA, Darcy PK, Smyth MJ, Stagg J (2013) CD73 promotes anthracycline resistance and poor prognosis in triple negative breast cancer. Proc Natl Acad Sci USA 110:11091–11096. https://doi.org/10.1073/pnas.1222251110 CrossRefPubMedPubMedCentral

36.

Ren ZH, Lin CZ, Cao W, Yang R, Lu W, Liu ZQ, Chen YM, Yang X, Tian Z, Wang LZ, Li J, Wang X, Chen WT, Ji T, Zhang CP (2016) CD73 is associated with poor prognosis in HNSCC. Oncotarget 7:61690–61702. https://doi.org/10.18632/oncotarget.11435 PubMedPubMedCentral

37.

James MF, Manchanda N, Gonzalez-Agosti C, Hartwig JH, Ramesh V (2001) The neurofibromatosis 2 protein product merlin selectively binds F-actin but not G-actin, and stabilizes the filaments through a lateral association. Biochem J 356:377–386CrossRefPubMedPubMedCentral

38.

James MF, Lelke JM, Maccollin M, Plotkin SR, Stemmer-Rachamimov AO, Ramesh V, Gusella JF (2008) Modeling NF2 with human arachnoidal and meningioma cell culture systems: NF2 silencing reflects the benign character of tumor growth. Neurobiol Dis 29:278–292. https://doi.org/10.1016/j.nbd.2007.09.002 CrossRefPubMed

39.

Stamenkovic I, Yu Q (2010) Merlin, a “magic” linker between the extracellular cues and intracellular signaling pathways that regulate cell motility, proliferation, and survival. Curr Protein Pept Sci 11:471–484CrossRefPubMedPubMedCentral

40.

Gao ZW, Dong K, Zhang HZ (2014) The roles of CD73 in cancer. BioMed Res Int 2014:460654. https://doi.org/10.1155/2014/460654 PubMedPubMedCentral

41.

Bowser JL, Blackburn MR, Shipley GL, Molina JG, Dunner K Jr, Broaddus RR (2016) Loss of CD73-mediated actin polymerization promotes endometrial tumor progression. J Clin Invest 126:220–238. https://doi.org/10.1172/jci79380 CrossRefPubMed

Titel: The expression of the MSC-marker CD73 and of NF2/Merlin are correlated in meningiomas
verfasst von: Elmar Kirches
Tabea Steffen
Natalie Waldt
Eva Hebert
Doreen Pachow
Annette Wilisch-Neumann
Gerburg Keilhoff
Thomas Schneider
Werner E. K. Braunsdorf
Jan-Peter Warnke
Christian Mawrin
Publikationsdatum: 21.02.2018
Verlag: Springer US
Erschienen in: Journal of Neuro-Oncology / Ausgabe 2/2018
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-018-2807-7

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

The expression of the MSC-marker CD73 and of NF2/Merlin are correlated in meningiomas

Abstract

Leitlinien kompakt für die Neurologie

Neu im Fachgebiet Neurologie

„Restriktion auf vier Wochen Therapie bei Schlaflosigkeit ist absurd!“

Stuhltransfusion könnte Fortschreiten von Parkinson-Symptomen bremsen

Frühe Tranexamsäure-Therapie nützt wenig bei Hirnblutungen

Sind Frauen die fähigeren Ärzte?

Update Neurologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2018

The utility of “low current” stimulation threshold of intraoperative electromyography monitoring in predicting facial nerve function outcome after vestibular schwannoma surgery: a prospective cohort study of 103 large tumors

Medulloblastoma with transitional features between Group 3 and Group 4 is associated with good prognosis

Risk of post-operative venous thromboembolism in patients with meningioma

Clinical prognostic value of the isocitrate dehydrogenase 1 single-nucleotide polymorphism rs11554137 in glioblastoma

Patterns of relapse for children with localized intracranial ependymoma

Cost-effectiveness of the long-term use of temozolomide for treating newly diagnosed glioblastoma in Germany

Leitlinien kompakt für die Neurologie

Neu im Fachgebiet Neurologie

„Restriktion auf vier Wochen Therapie bei Schlaflosigkeit ist absurd!“

Stuhltransfusion könnte Fortschreiten von Parkinson-Symptomen bremsen

Frühe Tranexamsäure-Therapie nützt wenig bei Hirnblutungen

Sind Frauen die fähigeren Ärzte?

Update Neurologie