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Matrix metalloproteinases in tumorigenesis: an evolving paradigm

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Abstract

Proteases are crucial for development, tissue remodeling, and tumorigenesis. Matrix metalloproteinases (MMPs) family, in particular, consists of more than 20 members with unique substrates and diverse function. The expression and activity of MMPs in a variety of human cancers have been intensively studied. MMPs have well-recognized roles in the late stage of tumor progression, invasion, and metastasis. However, increasing evidence demonstrates that MMPs are involved earlier in tumorigenesis, e.g., in malignant transformation, angiogenesis, and tumor growth both at the primary and metastatic sites. Recent studies also suggest that MMPs play complex roles in tumor progression. While most MMPs promote tumor progression, some of them may protect the host against tumorigenesis in a context-dependent manner. MMPs have been chosen as promising targets for cancer therapy on the basis of their aberrant up-regulation in malignant tumors and their ability to promote cancer metastasis. Although preclinical studies testing the efficacy of MMP suppression in tumor models were so encouraging, the results of clinical trials in cancer patients have been rather disappointing. Here, we review the complex roles of MMPs and their endogenous inhibitors such as tissue inhibitors of metalloproteinase in tumorigenesis and strategies in suppressing MMPs.

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References

  1. Bhowmick NA, Neilson EG, Moses HL (2004) Stromal fibroblasts in cancer initiation and progression. Nature 432:332–337

    Article  PubMed  CAS  Google Scholar 

  2. Stetler-Stevenson WG, Aznavoorian S, Liotta LA (1993) Tumor cell interactions with the extracellular matrix during invasion and metastasis. Annu Rev Cell Biol 9:541–573

    Article  PubMed  CAS  Google Scholar 

  3. Friedl P, Wolf K, Travel T (2008) The role of proteases in individual and collective cancer cell invasion. Cancer Res 68:7247–7249

    Article  PubMed  CAS  Google Scholar 

  4. Hojilla C, Wood G, Khokha R (2008) Inflammation and breast cancer. Metalloproteinases as common effectors of inflammation and extracellular matrix breakdown in breast cancer. Breast Cancer Res 10:205

    Article  PubMed  CAS  Google Scholar 

  5. Overall CM, Lopez-Otin C (2002) Strategies for MMP inhibition in cancer: innovations for the post-trial era. Nat Rev Cancer 2:657–672

    Article  PubMed  CAS  Google Scholar 

  6. Hu J, Van den Steen PE, Sang Q-X, Opdenakker G (2007) Matrix metalloproteinase inhibitors as therapy for inflammatory and vascular diseases. Nat Rev Drug Discov 6:480–498

    Article  PubMed  CAS  Google Scholar 

  7. Opdenakker G, Van den Steen PE, Van Damme J (2001) Gelatinase B: a tuner and amplifier of immune functions. Trends Immunol 22:571–579

    Article  PubMed  CAS  Google Scholar 

  8. Sato H, Seiki M (1996) Membrane-type matrix metalloproteinases (MT-MMPs) in tumor metastasis. J Biochem 119:209–215

    PubMed  CAS  Google Scholar 

  9. Sohail A, Sun Q, Zhao H, Bernardo MM, Cho JA, Fridman R (2008) MT4-(MMP17) and MT6-MMP (MMP25), a unique set of membrane-anchored matrix metalloproteinases: properties and expression in cancer. Cancer Metastasis Rev 27:289–302

    Article  PubMed  CAS  Google Scholar 

  10. Vincenti MP (2001) The matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) genes. Transcriptional and posttranscriptional regulation, signal transduction and cell-type-specific expression. Methods Mol Biol 151:121–148

    PubMed  CAS  Google Scholar 

  11. Borden P, Heller RA (1997) Transcriptional control of matrix metalloproteinases and the tissue inhibitors of matrix metalloproteinases. Crit Rev Eukaryot Gene Expr 7:159–178

    PubMed  CAS  Google Scholar 

  12. Brinckerhoff CE, Rutter JL, Benbow U (2000) Interstitial collagenases as markers of tumor progression. Clin Cancer Res 6:4823–4830

    PubMed  CAS  Google Scholar 

  13. Liacini A, Li WQ, Huang W, Dehnade F, Ahmad M, Zafarullah M (2003) Induction of matrix metalloproteinase-13 gene expression by TNF-α is mediated by MAP kinases, AP-1, and NF-κB transcription factors in articular chondrocytes. Exp Cell Res 288:208–217

    Article  PubMed  CAS  Google Scholar 

  14. Remacle AG, Rozanov DV, Fugere M, Day R, Strongin AY (2006) Furin regulates the intracellular activation and the uptake rate of cell surface-associated MT1-MMP. Oncogene 25:5648–5655

    Article  PubMed  CAS  Google Scholar 

  15. Rozanov DV, Hahn-Dantona E, Strickland DK, Strongin AY (2004) The low-density lipoprotein receptor-related protein LRP is regulated by membrane type-1 matrix metalloproteinase (MT1-MMP) proteolysis in malignant cells. J Biol Chem 279:4260–4268

    Article  PubMed  CAS  Google Scholar 

  16. Yang Z, Strickland DK, Bornstein P (2001) Extracellular matrix metalloproteinase 2 levels are regulated by the low-density lipoprotein-related scavenger receptor and thrombospondin 2. J Biol Chem 276:8403–8408

    Article  PubMed  CAS  Google Scholar 

  17. Douglas DA, Shi YE, Sang QA (1997) Computational sequence analysis of the tissue inhibitor of metalloproteinase family. J Protein Chem 16:237–255

    Article  PubMed  CAS  Google Scholar 

  18. Bigg HF, Shi YE, Liu YE, Steffensen B, Overall CM (1997) Specific, high affinity binding of tissue inhibitor of metalloproteinases-4 (TIMP-4) to the COOH-terminal hemopexin-like domain of human gelatinase A. J Biol Chem 272:15496–15500

    Article  PubMed  CAS  Google Scholar 

  19. Seiki M (1999) Membrane-type matrix metalloproteinases. APMIS 107:137–143

    Article  PubMed  CAS  Google Scholar 

  20. Strongin AY, Collier I, Bannikov G, Marmer BL, Grant GA, Goldberg GI (1995) Mechanism of cell surface activation of 72-kDa type IV collagenase. J Biol Chem 270:5331–5338

    Article  PubMed  CAS  Google Scholar 

  21. Hernandez-Barrantes S, Toth M, Bernardo MM et al (2000) Binding of active (57 kDa) membrane type 1-matrix metalloproteinase (MT1-MMP) to tissue inhibitor of metalloproteinase (TIMP)-2 regulates MT1-MMP processing and pro-MMP-2 activation. J Biol Chem 275:12080–12089

    Article  PubMed  CAS  Google Scholar 

  22. Butler GS, Butler MJ, Butler GS et al (1998) The TIMP2 membrane type 1 metalloproteinase “receptor” regulates the concentration and efficient activation of progelatinase A. J Biol Chem 273:871–880

    Article  PubMed  CAS  Google Scholar 

  23. Bigg HF, Morrison CJ, Butler GS et al (2001) Tissue inhibitor of metalloproteinases-4 inhibits but does not support the activation of gelatinase A via efficient inhibition of membrane type 1-matrix metalloproteinase. Cancer Res 61:3610–3618

    PubMed  CAS  Google Scholar 

  24. Cao J, Drews M, Lee HM, Conner C, Bahou WF, Zucker S (1998) The propeptide domain of membrane type 1 matrix metalloproteinase is required for binding of tissue inhibitor of metalloproteinases and for activation of pro-gelatinase A. J Biol Chem 273:34745–34752

    Article  PubMed  CAS  Google Scholar 

  25. Caterina JJ, Yamada S, Caterina NCM et al (2000) Inactivating mutation of the mouse tissue inhibitor of metalloproteinases-2 (Timp-2) gene alters ProMMP-2 activation. J Biol Chem 275:26416–26422

    Article  PubMed  CAS  Google Scholar 

  26. Itoh Y, Ito A, Iwata K, Tanzawa K, Mori Y, Nagase H (1998) Plasma membrane-bound tissue inhibitor of metalloproteinases (TIMP)-2 specifically inhibits matrix metalloproteinase 2 (gelatinase A) activated on the cell surface. J Biol Chem 273:24360–24367

    Article  PubMed  CAS  Google Scholar 

  27. Zhao H, Bernardo MM, Osenkowski P et al (2004) Differential inhibition of membrane type 3 (MT3)-matrix metalloproteinase (MMP) and MT1-MMP by tissue inhibitor of metalloproteinase (TIMP)-2 and TIMP-3 regulates pro-MMP-2 activation. J Biol Chem 279:8592–8601

    Article  PubMed  CAS  Google Scholar 

  28. English JL, Kassiri Z, Koskivirta I et al (2006) Individual Timp deficiencies differentially impact pro-MMP-2 activation. J Biol Chem 281:10337–10346

    Article  PubMed  CAS  Google Scholar 

  29. Knäuper V, López-Otin C, Smith B et al (1996) Cellular mechanisms for human procollagenase-3 (MMP-13) activation. J Biol Chem 271:17124–17131

    Article  PubMed  Google Scholar 

  30. Lubbe WJ, Zhou Z, Fu W et al (2006) Tumor epithelial cell matrix metalloproteinase 9 is a target for antimetastatic therapy in colorectal cancer. Clin Cancer Res 12:1876–1882

    Article  PubMed  CAS  Google Scholar 

  31. Samnegard A, Silveira A, Lundman P et al (2005) Serum matrix metalloproteinase-3 concentration is influenced by MMP-3 1612 5A/6A promoter genotype and associated with myocardial infarction. J Internal Med 258:41–419

    Article  CAS  Google Scholar 

  32. Poincloux R, Lizárraga F, Chavrier P (2009) Matrix invasion by tumour cells: a focus on MT1-MMP trafficking to invadopodia. J Cell Sci 122:3015–3024

    Article  PubMed  CAS  Google Scholar 

  33. Ducaa L, Alixb A, Hayea B, Debellea L (2004) Elastin as a matrikine. Crit Rev Oncol Hematol 49:235–244

    Article  Google Scholar 

  34. Koshikawa N, Minegishi T, Sharabi A, Quaranta V, Seiki M (2005) Membrane-type matrix metalloproteinase-1 (MT1-MMP) is a processing enzyme for human laminin gamma 2 chain. J Biol Chem 280:88–93

    PubMed  CAS  Google Scholar 

  35. Sadowski T, Dietrich S, Koschinsky F et al (2005) Matrix metalloproteinase 19 processes the laminin 5 gamma 2 chain and induces epithelial cell migration. Cell Mol Life Sci 62:870–880

    Article  PubMed  CAS  Google Scholar 

  36. Takafuji V, Forgues M, Unsworth E, Goldsmith P, Wang XW (2007) An osteopontin fragment is essential for tumor cell invasion in hepatocellular carcinoma. Oncogene 26:6361–6371

    Article  PubMed  CAS  Google Scholar 

  37. Manes S, Mira E, Barbacid MM et al (1997) Identification of insulin-like growth factor-binding protein-1 as a potential physiological substrate for human stromelysin-3. J Biol Chem 272:25706–25712

    Article  PubMed  CAS  Google Scholar 

  38. Manes S, Llorente M, Lacalle RA et al (1999) The matrix metalloproteinase-9 regulates the insulin-like growth factor-triggered autocrine response in DU-145 carcinoma cells. J Biol Chem 274:6935–6945

    Article  PubMed  CAS  Google Scholar 

  39. Rorive S, Berton A, D’Haene N et al (2008) Matrix metalloproteinase-9 interplays with the IGFBP2–IGFII complex to promote cell growth and motility in astrocytomas. Glia 56:1679–1690

    Article  PubMed  Google Scholar 

  40. Xu D, McKee CM, Cao Y, Ding Y, Kessler BM, Muschel RJ (2010) Matrix metalloproteinase-9 regulates tumor cell invasion through cleavage of protease nexin-1. Cancer Res 70:6988–6998

    Article  PubMed  CAS  Google Scholar 

  41. Fayard B, Bianchi F, Dey J et al (2009) The serine protease inhibitor protease nexin-1 controls mammary cancer metastasis through LRP-mediated MMP-9 expression. Cancer Res 69:5690–5698

    Article  PubMed  CAS  Google Scholar 

  42. Koshikawa N, Mizushima H, Minegishi T, Iwamoto R, Mekada E, Seiki M (2010) Membrane type 1-matrix metalloproteinase cleaves off the NH2-terminal portion of heparin-binding epidermal growth factor and converts it into a heparin-independent growth factor. Cancer Res 70:6093–6103

    Article  PubMed  CAS  Google Scholar 

  43. Golubkov VS, Chekanov AV, Cieplak P, Aleshin AE, Chernov AV, Zhu W, Radichev IA, Zhang D, Dong PD, Strongin AY (2010) The Wnt/planar cell polarity protein-tyrosine kinase-7 (PTK7) is a highly efficient proteolytic target of membrane type-1 matrix metalloproteinase: implications in cancer and embryogenesis. J Biol Chem 285:35740–35749

    Article  PubMed  CAS  Google Scholar 

  44. Sabbota AL, Kim H-RC, Zhe X, Fridman R, Bonfil RD, Cher ML (2010) Shedding of RANKL by tumor-associated MT1-MMP activates Src-dependent prostate cancer cell migration. Cancer Res 70:5558–5566

    Article  PubMed  CAS  Google Scholar 

  45. Nannuru KC, Futakuchi M, Varney ML, Vincent TM, Marcusson EG, Singh RK (2010) Matrix metalloproteinase (MMP)-13 regulates mammary tumor-induced osteolysis by activating MMP9 and transforming growth factor-beta signaling at the tumor-bone interface. Cancer Res 70:3494–3504

    Article  PubMed  CAS  Google Scholar 

  46. Bergers G, Brekken R, McMahon G et al (2000) Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol 2:737–744

    Article  PubMed  CAS  Google Scholar 

  47. Fang J, Shing Y, Wiederschain D et al (2000) Matrix metalloproteinase-2 is required for the switch to the angiogenic phenotype in a tumor model. Proc Natl Acad Sci USA 97:3884–3889

    Article  PubMed  CAS  Google Scholar 

  48. Eisenach PA, Roghi C, Fogarasi M, Murphy G, English WR (2010) MT1-MMP regulates VEGF-A expression through a complex with VEGFR-2 and Src. J Cell Sci 123:4182–4193

    Article  PubMed  CAS  Google Scholar 

  49. Ito T-K, Ishii G, Saito S et al (2009) Degradation of soluble VEGF receptor-1 by MMP-7 allows VEGF access to endothelial cells. Blood 113:2363–2369

    Article  PubMed  CAS  Google Scholar 

  50. Hawinkels LJ, Kuiper P, Wiercinska E et al (2010) Matrix metalloproteinase-14 (MT1-MMP)–mediated endoglin shedding inhibits tumor angiogenesis. Cancer Res 70:4141–4150

    Article  PubMed  CAS  Google Scholar 

  51. Patterson BC, Sang QA (1997) Angiostatin-converting enzyme activities of human matrilysin (MMP-7) and gelatinase B/Type IV collagenase (MMP-9). J Biol Chem 272:28823–28825

    Article  PubMed  CAS  Google Scholar 

  52. Lin HC, Chang JH, Jain S et al (2001) Matrilysin cleavage of corneal collagen type XVIII NC1 domain and generation of a 28-kDa fragment. Invest Ophthalmol Vis Sci 42:2517–2524

    PubMed  CAS  Google Scholar 

  53. Chang JH, Javier JAD, Chang GY, Oliveira H, Azar D (2005) Functional characterization of neostatins, the MMP-derived, enzymatic cleavage products of type XVIII collagen. FEBS Lett 579:3601–3606

    Article  PubMed  CAS  Google Scholar 

  54. Coussens LM, Raymond WW, Bergers G et al (1999) Inflammatory mast cells up-regulate angiogenesis during squamous epithelial carcinogenesis. Genes Devel 13:1382–1397

    Article  PubMed  CAS  Google Scholar 

  55. Zhang K, McQuibban GA, Silva C et al (2003) HIV-induced metalloproteinase processing of the chemokine stromal cell derived factor-1 causes neurodegeneration. Nat Neurosci 6:1064–1071

    Article  PubMed  CAS  Google Scholar 

  56. McQuibban GA, Butler GS, Gong JH et al (2001) Matrix metalloproteinase activity inactivates the CXC chemokine stromal cell-derived factor-1. J Biol Chem 276:43503–43508

    Article  PubMed  CAS  Google Scholar 

  57. Dean RA, Overall CM (2007) Proteomics discovery of metalloproteinase substrates in the cellular context by iTRAQ labeling reveals a diverse MMP-2 substrate degradome. Mol Cell Proteomics 6:611–623

    Article  PubMed  CAS  Google Scholar 

  58. Van den Steen PE, Proost P, Wuyts A, Van Damme J, Opdenakker G (2000) Neutrophil gelatinase B potentiates interleukin-8 tenfold by aminoterminal processing, whereas it degrades CTAP-III, PF-4, and GRO-alpha and leaves RANTES and MCP-2 intact. Blood 96:2673–2681

    PubMed  Google Scholar 

  59. Van den Steen PE, Wuyts A, Husson SJ, Proost P, Van Damme J, Opdenakker G (2003) Gelatinase B/MMP-9 and neutrophil collagenase/MMP-8 process the chemokines human GCP-2/CXCL6, ENA-78/CXCL5 and mouse GCP-2/LIX and modulate their physiological activities. Eur J Biochem 270:3739–3749

    Article  CAS  Google Scholar 

  60. Van den Steen PE, Husson SJ, Proost P, Van Damme J, Opdenakker G (2003) Carboxyterminal cleavage of the chemokines MIG and IP-10 by gelatinase B and neutrophil collagenase. Biochem Biophys Res Commun 310:889–896

    Article  PubMed  CAS  Google Scholar 

  61. Liao F, Rabin RL, Yannelli JR, Koniaris LG, Vanguri P, Farber JM (1995) Human Mig chemokine: biochemical and functional characterization. J Exp Med 182:1301–1314

    Article  PubMed  CAS  Google Scholar 

  62. McQuibban GA, Gong JH, Tam EM, McCulloch CA, Clark-Lewis I, Overall CM (2000) Inflammation dampened by gelatinase A cleavage of monocyte chemoattractant protein-3. Science 289:1202–1206

    Article  PubMed  CAS  Google Scholar 

  63. McQuibban GA, Gong JH, Wong JP, Wallace JL, Clark-Lewis I, Overall CM (2002) Matrix metalloproteinase processing of monocyte chemoattractant proteins generates CC chemokine receptor antagonists with anti-inflammatory properties in vivo. Blood 100:1160–1167

    PubMed  CAS  Google Scholar 

  64. Tam EM, Morrison CJ, Wu YI, Stack MS, Overall CM (2004) Membrane protease proteomics: isotope-coded affinity tag MS identification of undescribed MT1-matrix metalloproteinase substrates. Proc Natl Acad Sci USA 101:6917–6922

    Article  PubMed  CAS  Google Scholar 

  65. Tester AM, Cox JH, Connor AR et al (2007) LPS responsiveness and neutrophil chemotaxis in vivo require PMN MMP-8 activity. PLoS One 2:e312

    Article  PubMed  CAS  Google Scholar 

  66. Balbin M, Fueyo A, Tester AM et al (2003) Loss of collagenase-2 confers increased skin tumor susceptibility to male mice. Nat Genet 35:252–257

    Article  PubMed  CAS  Google Scholar 

  67. van den Steen PE, Proost P, Grillet B et al (2002) Cleavage of denatured natural collagen type II by neutrophil gelatinase B reveals enzyme specificity, post-translational modifications in the substrate, and the formation of remnant epitopes in rheumatoid arthritis. FASEB J 16:379–389

    Article  PubMed  Google Scholar 

  68. Cho A, Reidy MA (2002) Matrix metalloproteinase-9 is necessary for the regulation of smooth muscle cell replication and migration after arterial injury. Circ Res 91:845–851

    Article  PubMed  CAS  Google Scholar 

  69. Duong TD, Erickson CA (2004) MMP-2 plays an essential role in producing epithelial-mesenchymal transformations in the avian embryo. Dev Dyn 229:42–53

    Article  PubMed  CAS  Google Scholar 

  70. Xu J, Lamouille S, Derynck R (2009) TGF-β-induced epithelial to mesenchymal transition. Cell Res 19:156–172

    Article  PubMed  CAS  Google Scholar 

  71. Taki M, Verschueren K, Yokoyama K, Nagayama M, Kamata N (2006) Involvement of Ets-1 transcription factor in inducing matrix metalloproteinase-2 expression by epithelial-mesenchymal transition in human squamous carcinoma cells. Int J Oncol 28:487–496

    PubMed  CAS  Google Scholar 

  72. Lochter A, Galosy S, Muschler J, Freedman N, Werb Z, Bissell MJ (1997) Matrix metalloproteinase stromelysin-1 triggers a cascade of molecular alterations that leads to stable epithelial-to-mesenchymal conversion and a premalignant phenotype in mammary epithelial cells. J Cell Biol 139:1861–1872

    Article  PubMed  CAS  Google Scholar 

  73. Radisky DC, Levy DD, Littlepage LE et al (2005) Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability. Nature 436:123–127

    Article  PubMed  CAS  Google Scholar 

  74. Blavier L, Lazaryev A, Shi XH, Dorey FJ, Shackleford GM, DeClerck YA (2010) Stromelysin-1 (MMP-3) is a target and a regulator of Wnt1-induced epithelial–mesenchymal transition (EMT). Cancer Biol Ther 10:198–208

    Article  PubMed  CAS  Google Scholar 

  75. Jordà M, Olmeda D, Vinyals A, Valero E et al (2005) Upregulation of MMP-9 in MDCK epithelial cell line in response to expression of the Snail transcription factor. J Cell Sci 118:3371–3385

    Article  PubMed  CAS  Google Scholar 

  76. Ota I, Li X-Y, Hu Y, Weiss SJ (2009) Induction of a MT1-MMP and MT2-MMP-dependent basement membrane transmigration program in cancer cells by Snail1. Proc Natl Acad Sci USA 106:20318–20323

    Article  PubMed  CAS  Google Scholar 

  77. Limb GA, Matter K, Murphy G et al (2005) Matrix metalloproteinase-1 associates with intracellular organelles and confers resistance to lamin A/C degradation during apoptosis. Am J Pathol 166:1555–1563

    Article  PubMed  CAS  Google Scholar 

  78. Chetty C, Bhoopathi P, Lakka SS, Rao JS (2007) MMP-2 siRNA induced Fas//CD95-mediated extrinsic II apoptotic pathway in the A549 lung adenocarcinoma cell line. Oncogene 26:7675–7683

    Article  PubMed  CAS  Google Scholar 

  79. Ben-Yosef Y, Miller A, Shapiro S, Lahat N (2005) Hypoxia of endothelial cells leads to MMP-2-dependent survival and death. Am J Physiol Cell Physiol 289:C1321–C1331

    Article  PubMed  CAS  Google Scholar 

  80. Alexander CM, Howard EW, Bissell MJ, Werb Z (1996) Rescue of mammary epithelial cell apoptosis and entactin degradation by a tissue inhibitor of metalloproteinases-1 transgene. J Cell Biol 135:1669–1677

    Article  PubMed  CAS  Google Scholar 

  81. Thomasset N, Lochter A, Sympson CJ et al (1998) Expression of autoactivated stromelysin-1 in mammary glands of transgenic mice leads to a reactive stroma during early development. Am J Pathol 153:457–467

    Article  PubMed  CAS  Google Scholar 

  82. Kim E-M, Shin E-J, Choi JH et al (2010) Matrix metalloproteinase-3 is increased and participates in neuronal apoptotic signaling downstream of caspase-12 during endoplasmic reticulum stress. J Biol Chem 285:16444–16452

    Article  PubMed  CAS  Google Scholar 

  83. Powell WC, Fingleton B, Wilson CL, Boothby M, Matrisian LM (1999) The metalloproteinase matrilysin proteolytically generates active soluble Fas ligand and potentiates epithelial cell apoptosis. Curr Biol 9:1441–1447

    Article  PubMed  CAS  Google Scholar 

  84. Mitsiades N, Yu WH, Poulaki V, Tsokos M, Stamenkovic I (2001) Matrix metalloproteinase-7-mediated cleavage of Fas ligand protects tumor cells from chemotherapeutic drug cytotoxicity. Cancer Res 61:577–581

    PubMed  CAS  Google Scholar 

  85. Strand S, Vollmer P, van den Abeelen L et al (2004) Cleavage of CD95 by matrix metalloproteinase-7 induces apoptosis resistance in tumour cells. Oncogene 23:3732–3736

    Article  PubMed  CAS  Google Scholar 

  86. Almendro V, Ametller E, Garcia-Recio S et al (2009) The role of MMP7 and its cross-talk with the FAS/FASL system during the acquisition of chemoresistance to oxaliplatin. PLoS One 4:e4728

    Article  PubMed  CAS  Google Scholar 

  87. Fingleton B, Vargo-Gogola T, Crawford HC, Matrisian LM (2001) Matrilysin [MMP-7] expression selects for cells with reduced sensitivity to apoptosis. Neoplasia 3:459–468

    Article  PubMed  CAS  Google Scholar 

  88. Sans-Fons MG, Sole S, Sanfeliu C, Planas AM (2010) Matrix metalloproteinase-9 and cell division in neuroblastoma cells and bone marrow macrophages. Am J Pathol 177:2870–2885

    Article  PubMed  CAS  Google Scholar 

  89. Chintala SK, Zhang X, Austin JS, Fini ME (2002) Deficiency in matrix metalloproteinase gelatinase B (MMP-9) protects against retinal ganglion cell death after optic nerve ligation. J Biol Chem 277:47461–47468

    Article  PubMed  CAS  Google Scholar 

  90. Currie JC, Fortier S, Sina A, Galipeau J, Cao J, Annabi B (2007) MT1-MMP down-regulates the glucose 6-phosphate transporter expression in marrow stromal cells: a molecular link between pro-MMP-2 activation, chemotaxis, and cell survival. J Biol Chem 282:8142–8149

    Article  PubMed  CAS  Google Scholar 

  91. Fromigue O, Louis K, Wu E et al (2003) Active stromelysin-3 (MMP-11) increases MCF-7 survival in three-dimensional matrigel culture via activation of p42/p44 MAP-kinase. Int J Cancer 106:355–363

    Article  PubMed  CAS  Google Scholar 

  92. Abraham R, Schafer J, Rothe M, Bange J, Knyazev P, Ullrich A (2005) Identification of MMP-15 as an anti-apoptotic factor in cancer cells. J Biol Chem 280:34123–34132

    Article  PubMed  CAS  Google Scholar 

  93. Gutiérrez-Fernández A, Folgueras AR, Garabaya C et al (2008) Matrix metalloproteinase-8 functions as a metastasis suppressor through modulation of tumor cell adhesion and invasion. Cancer Res 68:2755–2763

    Article  PubMed  CAS  Google Scholar 

  94. Yang W, Arii S, Gorrin-Rivas MJ, Mori A, Onodera H, Imamura M (2001) Human macrophage metalloelastase gene expression in colorectal carcinoma and its clinicopathologic significance. Cancer 91:1277–1283

    Article  PubMed  CAS  Google Scholar 

  95. Cornelius LA, Nehring LC, Harding E et al (1998) Matrix metalloproteinases generate angiostatin: effects on neovascularization. J Immunol 161:6845–6852

    PubMed  CAS  Google Scholar 

  96. O’Reilly MS, Holmgren L, Shing Y et al (1994) Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 79:315–328

    Article  PubMed  Google Scholar 

  97. O’Reilly MS, Stetler-Stevenson WG, Folkman J, Moses MA (1999) Regulation of angiostatin production by matrix metalloproteinase-2 in a model of concomitant resistance. J Biol Chem 274:29568–29571

    Article  PubMed  Google Scholar 

  98. Pozzi A, Moberg PE, Miles LA, Wagner S, Soloway P, Gardner HA (2000) Elevated matrix metalloprotease and angiostatin levels in integrin-1 knockout mice cause reduced tumor vascularization. Proc Natl Acad Sci USA 97:2202–2207

    Article  PubMed  CAS  Google Scholar 

  99. Wen W, Moses MA, Wiederschain D, Arbiser JL, Folkman J (1999) The generation of endostatin is mediated by elastase. Cancer Res 59:6052–6056

    PubMed  CAS  Google Scholar 

  100. Jawad MU, Garamszegi N, Garamszegi SP et al (2010) Matrix metalloproteinase 1: role in sarcoma biology. PLoS One 5:e14250

    Article  PubMed  CAS  Google Scholar 

  101. Khokha R (1994) Suppression of the tumorigenic and metastatic abilities of murine B16–F10 melanoma cells in vivo by the overexpression of the tissue inhibitor of the metalloproteinases-1. J Natl Cancer Inst 86:299–304

    Article  PubMed  CAS  Google Scholar 

  102. Watanabe M, Takahashi Y, Ohta T, Mai M, Sasaki T, Seiki M (1996) Inhibition of metastasis in human gastric cancer cells transfected with tissue inhibitor of metalloproteinase 1 gene in nude mice. Cancer 77:1676–1680

    PubMed  CAS  Google Scholar 

  103. Ahonen M, Baker AH, Kahari V-M (1998) Adenovirus-mediated gene delivery of tissue inhibitor of metalloproteinases-3 inhibits invasion and induces apoptosis in melanoma cells. Cancer Res 58:2310–2315

    PubMed  CAS  Google Scholar 

  104. Brand K, Baker AH, Perez-Canto A et al (2000) Treatment of colorectal liver metastases by adenoviral transfer of tissue inhibitor of metalloproteinases-2 into the liver tissue. Cancer Res 60:5723–5730

    PubMed  CAS  Google Scholar 

  105. Sternlicht MD, Lochter A, Sympson CJ et al (1999) The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis. Cell 98:137–146

    Article  PubMed  CAS  Google Scholar 

  106. Coussens LM, Tinkle CL, Hanahan D, Werb Z (2000) MMP-9 supplied by bone marrow derived cells contributes to skin carcinogenesis. Cell 103:481–490

    Article  PubMed  CAS  Google Scholar 

  107. Docherty AJP, Lyons A, Smith BJ et al (1985) Sequence of human tissue inhibitor of metalloproteinases and its identity to erythroid-potentiating activity. Nature 318:66–69

    Article  PubMed  CAS  Google Scholar 

  108. Stetler-Stevenson WG, Bersch N, Golde DW (1992) Tissue inhibitor of metalloproteinase-2 (TIMP-2) has erythroid-potentiating activity. FEBS Lett 296:231–234

    Article  PubMed  CAS  Google Scholar 

  109. Bertaux B, Hornebeck W, Eisen AZ, Dubertret L (1991) Growth stimulation of human keratinocytes by tissue inhibitor of metalloproteinases. J Investig Dermatol 97:679–685

    Article  PubMed  CAS  Google Scholar 

  110. Hayakawa T, Yamashita K, Tanzawa K, Uchijima E, Iwata K (1992) Growth-promoting activity of tissue inhibitor of metalloproteinases-1 (TIMP-1) for a wide range of cells. A possible new growth factor in serum. FEBS Lett 298:29–32

    Article  PubMed  CAS  Google Scholar 

  111. Guedez L, Stetler-Stevenson WG, Wolff L et al (1998) In vitro suppression of programmed cell death of B cells by tissue inhibitor of metalloproteinases-1. J Clin Invest 102:2002–2010

    Article  PubMed  CAS  Google Scholar 

  112. Li G, Fridman R, Kim H-RC (1999) Tissue inhibitor of metalloproteinase-1 inhibits apoptosis of human breast epithelial cells. Cancer Res 59:6267–6275

    PubMed  CAS  Google Scholar 

  113. Jiang Y, Wang M, Celiker MY et al (2001) Stimulation of mammary tumorigenesis by systemic tissue inhibitor of matrix metalloproteinase 4 gene delivery. Cancer Res 61:2365–2370

    PubMed  CAS  Google Scholar 

  114. Bigelow RL, Williams BJ, Carroll JL, Daves LK, Cardelli JA (2009) TIMP-1 overexpression promotes tumorigenesis of MDA-MB-231 breast cancer cells and alters expression of a subset of cancer promoting genes in vivo distinct from those observed in vitro. Breast Cancer Res Treat 117:31–44

    Article  PubMed  CAS  Google Scholar 

  115. Kopitz C, Gerg M, Bandapalli OR et al (2007) Tissue inhibitor of metalloproteinases-1 promotes liver metastasis by induction of hepatocyte growth factor signaling. Cancer Res 67:8615–8623

    Article  PubMed  CAS  Google Scholar 

  116. Schrotzlmair F, Kopitz C, Halbgewachs B et al (2010) Tissue inhibitor of metalloproteinases-1-induced scattered liver metastasis is mediated by host-derived urokinase-type plasminogen activator. J Cell Mol Med 14:2760–2770

    Article  PubMed  CAS  Google Scholar 

  117. Seo DW, Li H, Guedez L et al (2003) TIMP-2 mediated inhibition of angiogenesis: an MMP-independent mechanism. Cell 114:171–180

    Article  PubMed  CAS  Google Scholar 

  118. Seo DW, Kim SH, Eom SH et al (2008) TIMP-2 disrupts FGF-2-induced downstream signaling pathways. Microvasc Res 76:145–151

    Article  PubMed  CAS  Google Scholar 

  119. Lee SJ, Tsang PS, Diaz TM, Wei BY, Stetler-Stevenson WG (2010) TIMP-2 modulates VEGFR-2 phosphorylation and enhances phosphodiesterase activity in endothelial cells. Lab Invest 90:374–382

    Article  PubMed  CAS  Google Scholar 

  120. Qi JH, Ebrahem Q, Moore N et al (2003) A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2. Nat Med 9:407–415

    Article  PubMed  CAS  Google Scholar 

  121. Tsagaraki I, Tsilibary EC, Tzinia AK (2010) TIMP-1 interaction with alphavbeta3 integrin confers resistance to human osteosarcoma cell line MG-63 against TNF-alpha-induced apoptosis. Cell Tissue Res 342:87–96

    Article  PubMed  CAS  Google Scholar 

  122. Jung KK, Liu XW, Chirco R, Fridman R, Kim HR (2006) Identification of CD63 as a tissue inhibitor of metalloproteinase-1 interacting cell surface protein. EMBO J 25:3934–3942

    Article  PubMed  CAS  Google Scholar 

  123. Wang X, Fu X, Brown PD, Crimmin MJ, Hoffman RM (1994) Matrix metalloproteinase inhibitor BB-94 (batimastat) inhibits human colon tumor growth and spread in a patient-like orthotopic model in nude mice. Cancer Res 54:4726–4728

    PubMed  CAS  Google Scholar 

  124. Bu W, Tang ZY, Sun FX et al (1998) Effects of matrix metalloproteinase inhibitor BB-94 on liver cancer growth and metastasis in a patient-like orthotopic model LCI-D20. Hepatogastroenterology 45:1056–1061

    PubMed  CAS  Google Scholar 

  125. Taraboletti G, Garofalo A, Belotti D et al (1995) Inhibition of angiogenesis and murine hemangioma growth by batimastat, a synthetic inhibitor of matrix metalloproteinases. J Natl Cancer Inst 87:293–298

    Article  PubMed  CAS  Google Scholar 

  126. Watson SA, Morris TM, Robinson G, Crimmin MJ, Brown PD, Hardcastle JD (1995) Inhibition of organ invasion by the matrix metalloproteinase inhibitor batimastat (BB-94) in two human colon carcinoma metastasis models. Cancer Res 55:3629–3633

    PubMed  CAS  Google Scholar 

  127. Eccles SA, Box GM, Court WJ, Bone EA, Thomas W, Brown PD (1996) Control of lymphatic and hematogenous metastasis of a rat mammary carcinoma by the matrix metalloproteinase inhibitor batimastat (BB-94). Cancer Res 56:2815–2822

    PubMed  CAS  Google Scholar 

  128. Giavazzi R, Garofalo A, Ferri C et al (1998) Batimastat, a synthetic inhibitor of matrix metalloproteinases, potentiates the antitumor activity of cisplatin in ovarian carcinoma xenografts. Clin Cancer Res 4:985–992

    PubMed  CAS  Google Scholar 

  129. Prontera C, Mariani B, Rossi C, Poggi A, Rotilio D (1999) Inhibition of gelatinase A (MMP-2) by batimastat and captopril reduces tumor growth and lung metastases in mice bearing Lewis lung carcinoma. Int J Cancer 81:761–766

    Article  PubMed  CAS  Google Scholar 

  130. Holst-Hansen C, Low JA, Stephens RW et al (2001) Increased stromal expression of murine urokinase plasminogen activator in a human breast cancer xenograft model following treatment with the matrix metalloprotease inhibitor, batimastat. Breast Cancer Res Treat 68:225–237

    Article  PubMed  CAS  Google Scholar 

  131. Kruger A, Soeltl R, Sopov I et al (2001) Hydroxamate-type matrix metalloproteinase inhibitor batimastat promotes liver metastasis. Cancer Res 61:1272–1275

    PubMed  CAS  Google Scholar 

  132. Hidalgo M, Eckhardt SG (2001) Development of matrix metalloproteinase inhibitors in cancer therapy. J Natl Cancer Inst 93:178–193

    Article  PubMed  CAS  Google Scholar 

  133. Maekarva K, Sato H, Furukawa M, Yoshizaki T (2002) Inhibition of cervical lymph node metastasis by marimastat (BB-2516) in an orthotopic oral squamous cell carcinoma implantation model. Clin Exp Metastasis 19:513–518

    Article  Google Scholar 

  134. Kimata M, Otani Y, Kubota T et al (2002) Matrix metalloproteinase inhibitor, marimastat, decreases peritoneal spread of gastric carcinoma in nude mice. Jpn J Cancer Res 93:834–841

    Article  PubMed  CAS  Google Scholar 

  135. Shepherd FA, Giaccone G, Seymour L et al (2002) Prospective, randomized, double-blind, placebo-controlled trial of marimastat after response to first-line chemotherapy in patients with small-cell lung cancer: a trial of the National Cancer Institute of Canada-Clinical Trials Group and the European Organization for Research and Treatment of Cancer. J Clin Oncol 20:4434–4439

    Article  PubMed  CAS  Google Scholar 

  136. Steward WP, Thomas AL (2000) Marimastat: the clinical development of a matrix metalloproteinase inhibitor. Expert Opin Investig Drugs 9:2913–2922

    Article  PubMed  CAS  Google Scholar 

  137. Bramhall SR, Rosemurgy A, Brown PD, Bowry C, Buckels JAC (2001) Marimastat as first-line therapy for patients with unresectable pancreatic cancer: a randomized trial. J Clin Oncol 19:3447–3455

    PubMed  CAS  Google Scholar 

  138. Bramhall SR, Schulz J, Nemunaitis J, Brown PD, Baillet M, Buckels JA (2002) A double-blind placebo-controlled, randomised study comparing gemcitabine and marimastat with gemcitabine and placebo as first line therapy in patients with advanced pancreatic cancer. British J Cancer 87:161–167

    Article  CAS  Google Scholar 

  139. Scatena R (2000) Prinomastat, a hydroxamate-based matrix metalloproteinase inhibitor. A novel pharmacological approach for tissue remodelling-related diseases. Expert Opin Investig Drugs 9:2159–2165

    Article  PubMed  CAS  Google Scholar 

  140. Liu J, Tsao MS, Pagura M et al (2003) Early combined treatment with carboplatin and the MMP inhibitor, prinomastat, prolongs survival and reduces systemic metastasis in an aggressive orthotopic lung cancer model. Lung Cancer 42:335–344

    Article  PubMed  Google Scholar 

  141. Alves F, Borchers U, Padge B et al (2001) Inhibitory effect of a matrix metalloproteinase inhibitor on growth and spread of human pancreatic ductal adenocarcinoma evaluated in an orthotopic severe combined immunodeficient (SCID) mouse model. Cancer Lett 165:161–170

    Article  PubMed  CAS  Google Scholar 

  142. Shalinsky DR, Brekken J, Zou H et al (1999) Marked antiangiogenic and antitumor efficacy of AG3340 in chemoresistant human non-small cell lung cancer tumors: single agent and combination chemotherapy studies. Clin Cancer Res 5:1905–1917

    PubMed  CAS  Google Scholar 

  143. Price A, Shi Q, Morris D et al (1999) Marked inhibition of tumor growth in a malignant glioma tumor model by a novel synthetic matrix metalloproteinase inhibitor AG3340. Clin Cancer Res 5:845–854

    PubMed  CAS  Google Scholar 

  144. Frederick R, Ahmann FS, Mercier R et al (2001) Interim results of a phase III study of the matrix metalloprotease inhibitor prinomastat in patients having metastatic, hormone refractory prostate cancer (HRPC). Proc Am Soc Clin Oncol 20:abstract 692

    Google Scholar 

  145. Bissett D, O’Byrne KJ, von Pawel J et al (2005) Phase III study of matrix metalloproteinase inhibitor prinomastat in non-small-cell lung cancer. J Clin Oncol 23:842–849

    Article  PubMed  CAS  Google Scholar 

  146. Moore MJ, Hamm J, Dancey J et al (2003) Comparison of gemcitabine versus the matrix metalloproteinase inhibitor BAY 12–9566 in patients with advanced or metastatic adenocarcinoma of the pancreas: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 21:3296–3302

    Article  PubMed  CAS  Google Scholar 

  147. Hoffman A, Qadri B, Frant J et al (2008) Carbamoylphosphonate matrix metalloproteinase inhibitors 6: cis-2-aminocyclohexylcarbamoylphosphonic acid, a novel orally active antimetastatic matrix metalloproteinase-2 selective inhibitor-synthesis and pharmacodynamic and pharmacokinetic analysis. J Med Chem 51:1406–1414

    Article  PubMed  CAS  Google Scholar 

  148. Chiappori AA, Eckhardt SG, Bukowski R et al (2007) A phase I pharmacokinetic and pharmacodynamic study of S-3304, a novel matrix metalloproteinase inhibitor, in patients with advanced and refractory solid tumors. Clin Cancer Res 13:2091–2099

    Article  PubMed  CAS  Google Scholar 

  149. Maquoi E, Sounni NE, Devy L et al (2004) Anti-invasive, antitumoral, and antiangiogenic efficacy of a pyrimidine-2, 4, 6-trione derivative, an orally active and selective matrix metalloproteinases inhibitor. Clin Cancer Res 10:4038–4047

    Article  PubMed  CAS  Google Scholar 

  150. Engel CK, Pirard P, Schimanski S et al (2005) Tumor epithelial cell matrix metalloproteinase 9 is a target for antimetastatic therapy in colorectal cancer. Chem Biol 12:181–189

    Article  PubMed  CAS  Google Scholar 

  151. Lauer-Fields JL, Whitehead JK, Li S et al (2008) Selective modulation of matrix metalloproteinase 9 (MMP-9) functions via exosite inhibition. J Biol Chem 283:20087–20095

    Article  PubMed  CAS  Google Scholar 

  152. Ikejirim M, Bernardo MM, Bonfil RD et al (2005) Potent mechanism-based inhibitors for matrix metalloproteinases. J Biol Chem 280:33992–34002

    Article  CAS  Google Scholar 

  153. Tao P, Fisher JF, Shi Q et al (2009) Matrix metalloproteinase 2 (MMP2) inhibition: QM/MM studies of the inhibition mechanism of SB-3CT and its analog. Biochemistry 48:9839–9847

    Article  PubMed  CAS  Google Scholar 

  154. Krüger A, Arlt MJE, Gerg M et al (2005) Antimetastatic activity of a novel mechanism-based gelatinase inhibitor. Cancer Res 65:3523–3526

    Article  PubMed  Google Scholar 

  155. Bonfil RD, Sabbota A, Nabha S et al (2006) Inhibition of human prostate cancer growth, osteolysis and angiogenesis in a bone metastasis model by a novel mechanism-based selective gelatinase inhibitor. Int J Cancer 118:2721–2726

    Article  PubMed  CAS  Google Scholar 

  156. Devy L, Huang L, Naa L et al (2009) Selective inhibition of matrix metalloproteinase-14 blocks tumor growth, invasion, and angiogenesis. Cancer Res 69:1517–1526

    Article  PubMed  CAS  Google Scholar 

  157. Lukkonen A, Sorsa T, Salo T et al (2000) Down-regulation of trypsinogen-2 expression by chemically modified tetracyclines: association with reduced cancer cell migration. Int J Cancer 86:577–581

    Article  PubMed  CAS  Google Scholar 

  158. Nair RR, Avila H, Ma X et al (2008) A novel high-throughput screening system identifies a small molecule repressive for matrix metalloproteinase-9 expression. Mol Pharmacol 73:919–929

    Article  PubMed  CAS  Google Scholar 

  159. Toda D, Ota T, Tsukuda K et al (2006) Gefitinib decreases the synthesis of matrix metalloproteinase and the adhesion to extracellular matrix proteins of colon cancer cells. Anticancer Res 26:129–134

    PubMed  CAS  Google Scholar 

  160. Wei LH, Lai KP, Chen CA et al (2005) Arsenic trioxide prevents radiation-enhanced tumor invasiveness and inhibits matrix metalloproteinase-9 through downregulation of nuclear factor kappaB. Oncogene 24:390–398

    Article  PubMed  CAS  Google Scholar 

  161. Ito H, Duxbury M, Benoit E et al (2004) Prostaglandin E2 enhances pancreatic cancer invasiveness through an Ets-1-dependent induction of matrix metalloproteinase-2. Cancer Res 64:7439–7446

    Article  PubMed  CAS  Google Scholar 

  162. Blazquez C, Salazar M, Carracedo A et al (2008) Cannabinoids inhibit glioma cell invasion by down-regulating matrix metalloproteinase-2 expression. Cancer Res 68:1945–1952

    Article  PubMed  CAS  Google Scholar 

  163. Kim SY, Jung SH, Kim HS (2005) Curcumin is a potent broad spectrum inhibitor of matrix metalloproteinase gene expression in human astroglioma cells. Biochem Biophys Res Commun 337:510–516

    Article  PubMed  CAS  Google Scholar 

  164. Gabriely G, Wurdinger T, Kesari S et al (2008) MicroRNA 21 promotes glioma invasion by targeting matrix metalloproteinase regulators. Mol Cell Biol 28:5369–5380

    Article  PubMed  CAS  Google Scholar 

  165. Chan JA, Krichevsky AM, Kosik KS (2005) MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 65:6029–6033

    Article  PubMed  CAS  Google Scholar 

  166. Volinia S, Calin GA, Liu CG et al (2006) A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA 103:2257–2261

    Article  PubMed  CAS  Google Scholar 

  167. Bao BY, Yeh SD, Lee YF (2006) 1alpha, 25-dihydroxyvitamin D3 inhibits prostate cancer cell invasion via modulation of selective proteases. Carcinogenesis 27:32–42

    Article  PubMed  CAS  Google Scholar 

  168. Sloane BF, Sameni M, Podgorski I et al (2006) Functional imaging of tumor proteolysis. Ann Rev Pharmacol Toxicol 46:301–315

    Article  CAS  Google Scholar 

  169. Martin MD, Carter KJ, Jean-Philippe SR et al (2008) Effect of ablation or inhibition of stromal matrix metalloproteinase-9 on lung metastasis in a breast cancer model is dependent on genetic background. Cancer Res 68:6251–6259

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The work in the authors’ lab was supported by the National Natural Science Foundation of China (Grants 30900554 and 30973435).

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Authors and Affiliations

  1. State Key Laboratory of Biotherapy, Section of Signal Transduction and Molecular Targeted Therapy, West China Hospital, Sichuan University, Chengdu, China

    Hui Hua, Minjing Li, Yancun Yin & Yangfu Jiang

  2. Cancer Center, West China Hospital, Sichuan University, Chengdu, China

    Ting Luo

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  1. Hui Hua
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  2. Minjing Li
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Correspondence to Yangfu Jiang.

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Hua, H., Li, M., Luo, T. et al. Matrix metalloproteinases in tumorigenesis: an evolving paradigm. Cell. Mol. Life Sci. 68, 3853–3868 (2011). https://doi.org/10.1007/s00018-011-0763-x

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  • DOI: https://doi.org/10.1007/s00018-011-0763-x

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