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Matrix Metalloproteinases and Cancer Cell Invasion/Metastasis

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The Tumor Microenvironment

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

A wealth of knowledge has accumulated over the past four decades on the importance of matrix metalloproteinases (MMPs) in cancer induction, invasion, and metastasis. This chapter aims to provide the reader with recent information to help understand the disconnect between experimental observations implicating the crucial role of MMPs in cancer progression and the historic failure of several broad-spectrum MMP inhibitors in clinical drug trials in advanced cancer. The chemistry and biology of the large MMP family and tissue inhibitors of MMPs (TIMPs) will be summarized. Complexity of MMP function in cancer will be described with an emphasis on pericellular cleavage of extracellular matrix (ECM) and non-ECM substrates. Production of MMPs by stromal cells within a tumor, as well as cancer cells, is well established. Anticancer effects of selected in MMPs are described. The study of cell migration within a three-dimensional collagen matrix has been responsible for broadening our understanding of cancer progression. The involvement of MMPs in the transition from noninvasive to invasive, metastatic cancer, and an emphasis on epithelial-to-mesenchymal transition (EMT) will be presented. New approaches to improve the specificity of MMP inhibitors for use in future clinical trials are discussed.

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References

  • Agrawal A et al (2008) Zinc-binding groups modulate selective inhibition of MMPs. Chem Med Chem 3:812–820

    PubMed  CAS  Google Scholar 

  • Ahn G-O, Brown JM (2008) Matrix metalloproteinase-9 is required for tumor vasculogenesis but not for angiogenesis: role of bone marrow-derived myelomonocytes. Cancer Cell 13:193–205

    Article  PubMed  CAS  Google Scholar 

  • Akhurst RJ, Derynck R (2001) TGF-beta signaling in cancer – a double-edged sword. Trends Cell Biol 11:S44–S51

    PubMed  CAS  Google Scholar 

  • Baker AH, Edwards DR, Murphy G (2002) Metalloproteinase inhibitors: biologic actions and therapeutic opportunities. J Cell Sci 115:3719–3727

    Article  PubMed  CAS  Google Scholar 

  • Balbin M 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 

  • Basset P et al (1990) A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas. Nature 348:699–704

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Birkedal-Hansen H (1995) Proteolytic remodeling of extracellular matrix. Curr Opin Cell Biol 7:728–735

    Article  PubMed  CAS  Google Scholar 

  • Bjorklund M, Heikkila P, Koivunen E (2004) Peptide inhibition of catalytic and noncatalytic activities of matrix metaalloproteinase-9 blocks tumor cell migration and invasion. J Biol Chem 279:29589–29597

    Article  PubMed  CAS  Google Scholar 

  • Blackburn JS, Brinkerhoff CE (2008) Matrix metalloproteinase-1 and thrombin differentially activate gene expression in endothelial cells via PAR-1 and promote angiogenesis. Am J Pathol 173:1736–1746

    Article  PubMed  CAS  Google Scholar 

  • Boire A et al (2005) PAR-1 is a matrix metalloproteinase-1 receptor that promotes invasion and tumorigenesis of breast cancer cells. Cell 120:303–313

    Article  PubMed  CAS  Google Scholar 

  • Bonnomet A et al (2008) The E-cadherin-repressed hNanos1 gene induces tumor cell invasion by upregulating MT1-MMP expression. Oncogene 27:3692–3699

    Article  PubMed  CAS  Google Scholar 

  • Brabletz T et al (2001) Variable beta-catenin expression in colorectal cancers indicates tumor progeression driven by the microenvironment. Proc Natl Acad Sci U S A 98:10356–10361

    Article  PubMed  CAS  Google Scholar 

  • Butler GS et al (1998) The TIMP-2 membrane type 1 metalloproteinase “receptor” regulates the concentration and efficiency of progelatinase A. A kinetic study. J Biol Chem 273: 871–880

    Article  PubMed  CAS  Google Scholar 

  • Cao J et al (2008) Membrane type I matrix metalloproteinase induces epithelial-to-mesenchymal transition in prostate cancer. J Biol Chem 283:6232–6240

    Article  PubMed  CAS  Google Scholar 

  • Cao J et al (1998) The propeptide domain of membrane type I 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 

  • Clark ES et al (2007) Cortactin is an essential regulator of matrix metalloproteinase secretion and extracellular matrix degradation in invadopodia. Cancer Res 67:4227–4235

    Article  PubMed  CAS  Google Scholar 

  • Coussens L, Fingleton B, Matrisian L (2002) Matrix metalloproteinase inhibitors and cancer: Trials and tribulations. Science 295:2387–2392

    Article  PubMed  CAS  Google Scholar 

  • Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860–867

    Article  PubMed  CAS  Google Scholar 

  • Dean RA, Overall CM (2007) Proteomics discovery of metalloproteinase substrates in the cellular context by iTRACTM labeling reveals a diverse MMP-2 substrate degradome. Mol Cell Proteomics 6:611–621

    Article  PubMed  CAS  Google Scholar 

  • Della Porta P et al (1999) Combined treatment with serine protease inhibitor aprotonin and matrix metalloproteinase inhibitor Batimastat (BB-94) does not prevent invasion of human esophageal and ovarian carcinoma cells in vitro. Anticancer Res 19:3809–3816

    PubMed  CAS  Google Scholar 

  • Desai B, Ma T, Chellaiah MA (2008) Invadopodia and matrix degradation: a new property of prostate cancer cells during migration and invasion. J Biol Chem 283:13856–13866

    Article  PubMed  CAS  Google Scholar 

  • Devy L et al (2009) Selective inhibitor of matrix metalloproteinase-14 blocks tumor growth, invasion, and angiogenesis. Cancer Res 69: 1517–1524

    Article  PubMed  CAS  Google Scholar 

  • Dufour A et al (2010) Critical role of MMP-9 dimers in cell migration (submitted for publication)

    Google Scholar 

  • Dufour A et al (2008) Role of the hemopexin domain of matrix metalloproteinases in cell migration. J Cell Physiol 217:643–651

    Article  PubMed  CAS  Google Scholar 

  • Erler JT et al (2009) Hypoxia-induce lysyl oxidas is a critical mediator of bone marrow cell recruitment to form the premetastatic niche. Cancer Cell 15:35–44

    Article  PubMed  CAS  Google Scholar 

  • Ezhilarasan E et al (2009) The hemopexin domain of MMP-9 inhibits angiogenesis and retards growth of intracranial glioblastoma xenografts in nude mice. Int J Cancer 124:306–315

    Article  PubMed  CAS  Google Scholar 

  • Fu X, Parks WC, Heinecke JW (2008) Activation and silencing of matrix metalloproteinases. Cell Dev Biol 19:2–13

    Article  CAS  Google Scholar 

  • Gaggioli C et al (2007) Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells. Nat Cell Biol 9:1392–1400

    Article  PubMed  CAS  Google Scholar 

  • Goldberg GI et al (1989) Human 72-kilodalton type IV collagenase forms a complex with a tissue inhibitor of metalloproteinases designated TIMP-2. Proc Natl Acad Sci U S A 86:8207–8211

    Article  PubMed  CAS  Google Scholar 

  • Gross J, Lapiere CM (1962) Collagenolytic activity in amphibian tissues; a tissue culture assay. Proc Natl Acad Sci U S A 48:1014–1022

    Article  PubMed  CAS  Google Scholar 

  • Guo H et al (2000) EMMPRIN (CD147), an inducer of matrix metalloproteinase synthesis, also binds interstitial collagenase to the tumor cell surface. Cancer Res 60:888–891

    PubMed  CAS  Google Scholar 

  • Gupta GP et al (2007) Mediators of vascular remodelling co-opted for sequential steps in lung metastasis. Nature 446:765–770

    Article  PubMed  CAS  Google Scholar 

  • Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70

    Article  PubMed  CAS  Google Scholar 

  • Hillon J et al (2009) Upregulation of MMP-2 by HMGA1 promotes transformation in undifferentiated, large-cell lung cancer. Mol Cancer Res 7:1803–1812

    Article  CAS  Google Scholar 

  • Hirasuka S et al (2006) Tumor-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis. Nat Cell Biol 8:1369–1375

    Article  CAS  Google Scholar 

  • Hotary KB et al (2003) Membrane type I matrix metalloproteinase usurps tumor growth control imposed by the three-dimensional extracellular matrix. Cell 114:33–45

    Article  PubMed  CAS  Google Scholar 

  • Howard EW, Bullen EC, Banda MJ (1991) Regulation of the autoactivation of human 72-kDa progelatinase by tissue inhibitor of metalloproteinases-2. J Biol Chem 266:13064–13069

    PubMed  CAS  Google Scholar 

  • Ikejiri M et al (2006) Design, synthesis, and evaluation of a mechanism-based inhibitor for gelatinase A. J Org Chem 70:5709–5712

    Article  CAS  Google Scholar 

  • Itoh Y, Seiki M (2006) MT1-MMP: a potent modifier of pericellular microenvironment. J Cell Physiol 206:1–8

    Article  PubMed  CAS  Google Scholar 

  • Kalluri R, Nielson EG (2003) Epithelial–mesenchymal transition and its implications for fibrosis. J Clin Invest 112:1776–1784

    PubMed  CAS  Google Scholar 

  • Kang Y, Massague J (2004) Epithelial–mesenchymal transitions: twist in development and metastasis. Cell 118:277–279

    Article  PubMed  CAS  Google Scholar 

  • Kaplan RN, Rafi S, Lyden D (2006) Preparing the soil: the premetastatic niche. Cancer Res 66:11089–11093

    Article  PubMed  CAS  Google Scholar 

  • Kruger A, Kates RE, Edwards DR (2010) Avoiding spam in the proteolytic internet: Future strategies for anti-metastatic MMP-inhibition. Biochim Biophys Acta 1803:95–102

    Article  PubMed  CAS  Google Scholar 

  • Lehti K et al (2005) An MT-MMP-PDGF receptor-beta axis regulates mural cell investment of themicrovasculature. Genes Dev 19:979–991

    Article  PubMed  CAS  Google Scholar 

  • Liotta LA et al (1980) Metastatic potential correlates with enzymatic degradation of basement membrane collogen. Nature 284:67–68

    Article  PubMed  CAS  Google Scholar 

  • Lopez-Otin C, Bond JS (2008) Proteases: multifunctional enzymes in life and disease. J Biol Chem 283:30433–30437

    Article  PubMed  CAS  Google Scholar 

  • Lui D, Hornsby PJ (2007) Senescent human fibroblasts increase the early growth of xenograft tumors via matrix metalloproteinase secretion. Cancer Res 67:3117–3126

    Article  CAS  Google Scholar 

  • Maquoi E et al (2000) Membrane type I matrix metalloproteinase-associated degradation of tissue inhibitor of metalloproteinase 2 in human tumor cell lines. J Biol Chem 275:11368–11378

    Article  PubMed  CAS  Google Scholar 

  • Martin MD, Matrisian LM (2007) The other side of MMPs: protective roles in tumor progression. Cancer Metastasis Rev 26:717–724

    Article  PubMed  CAS  Google Scholar 

  • Mazzone M et al (2004) Intracellular processing and activation of membrane type 1-matrix metalloprotease depends on its partitioning into lipid domains. J Cell Sci 117:6275–6287

    Article  PubMed  CAS  Google Scholar 

  • McQuibban GA 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 

  • Minn AJ et al (2005) Genes that mediate breast cancer metastasis to lung. Nature 436:518–524

    Article  PubMed  CAS  Google Scholar 

  • Mochizuki S, Okada Y (2007) ADAMs in cancer cell proliferation and progression. Cancer Sci 98:621–628

    Article  PubMed  CAS  Google Scholar 

  • Morgunova E et al (2002) Structural insight into the complex formation of latent matrix metalloproteinase 2 with tissue inhibitor of metalloproteinase 2. Proc Natl Acad Sci 99:7414–7419

    Article  PubMed  CAS  Google Scholar 

  • Nagase H, Woessner F (1999) Matrix metalloproteinases. J Biol Chem 274:21491–21494

    Article  PubMed  CAS  Google Scholar 

  • Nelson AR et al (2000) Matrix metalloproteinases: biologic activity and clinical implications. J Clin Oncol 18:1135–1139

    PubMed  CAS  Google Scholar 

  • Noel A et al (1997) Emerging roles for proteinases in cancer. Invasion Metastasis 17:221–239

    PubMed  CAS  Google Scholar 

  • Noel A, Jost M, Maquoi E (2008) Matrix metalloproteinases at cancer tumor–host interface. Semin Cell Dev Biol 19:52–60

    Article  PubMed  CAS  Google Scholar 

  • O’Reilly MS et al (1994) Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastasis by a Lewis lung carcinoma. Cell 79:315–328

    Article  PubMed  Google Scholar 

  • Overall CM, Kleifeld O (2006a) Toward third generation matrix metalloproteinase inhibitors for cancer research. Br J Cancer 94:941–946

    Article  PubMed  CAS  Google Scholar 

  • Overall CM, Kleifeld O (2006b) Validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy. Nat Rev Cancer 6:227–239

    Article  PubMed  CAS  Google Scholar 

  • Overall CM et al (2004) Protease degradomics: mass spectroscopy discovery of protease substrates and the CLIP-CHIP, a dedicated DNA microarray of all human proteases and inhibitors. Biol Chem 385:493–504

    Article  PubMed  CAS  Google Scholar 

  • Packard BZ et al (2009) Direct visualization of protease activity on cells migrating in three-dimensions. Matrix Biol 28:3–10

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Palavalli LH et al (2009) Analysis of the matrix metalloproteinase family reveals that MMP8 is often mutated in melanoma. Nat Genet 41:518–520

    Article  PubMed  CAS  Google Scholar 

  • Partridge JJ et al (2007) Functional analysis of MMPs and TIMPs differentially expressed by variants of human HT-1080 fibrosarcoma exhibiting high and low levels of intravasation and metastasis. J Biol Chem

    Google Scholar 

  • Pavlaki M, Zucker S (2003) Matrix metalloproteinase inhibitors (MMPIs): the beginning of phase I or the termination of phase III clinical trials. Cancer Metastasis Rev 22:177–203

    Article  PubMed  CAS  Google Scholar 

  • Poincloux R, Lizarraga 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 

  • Polette M et al (1996) MT-MMP expression and localization in human lung and breast cancer. Virchows Arch 428:29–35

    Article  PubMed  CAS  Google Scholar 

  • Powell WC et al (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 

  • Qian LW et al (2002) Radiation induced increase in invasive potential of human pancreatic cancer cells and its blockade by matrix metalloproteinase inhibitor. Clin Cancer Res 8:1223–1227

    PubMed  CAS  Google Scholar 

  • Radisky DC et al (2005) Rac1b and reactive oxygen species mediate MMP-3 induced EMT and genomic instability. Nature 463:123–127

    Article  CAS  Google Scholar 

  • Radjabi A et al (2008) Thrombin induces tumor invasion through the induction and association of matrix metalloproteinase-9 and beta1-integrin on the cell surface. J Biol Chem 283:2822–2834

    Article  PubMed  CAS  Google Scholar 

  • Rowe RG et al (2009) Mesenchymal cells reactivate Snail 1 expression to drive three-dimensional invasion programs. J Cell Biol 184:399–408

    Article  PubMed  CAS  Google Scholar 

  • Rowe RG, Weiss SJ (2008) Breaching the basement membrane: who, when and how? Trends Cell Biol 18:560–574

    Article  PubMed  CAS  Google Scholar 

  • Sabeh F, Shimizu-Hirota R, Weiss SJ (2009) Protease-dependent versus-independent cancer invasion programs: three dimensional amoeboid movement revisited. J Cell Biol 185:11–19

    Article  PubMed  CAS  Google Scholar 

  • Samanna V et al (2007) Actin polymerization modulates CD44 surface expression, MMP-9 activation, and osteoclast function. J Cell Physiol 213:710–720

    Article  PubMed  CAS  Google Scholar 

  • Sanz-Moreno V et al (2008) Rac activation and inactivation control plasticity of tumor cell movement. Cell 135:510–523

    Article  PubMed  CAS  Google Scholar 

  • Sato H et al (1994) A matrix metalloproteinase expressed on the surface of invasive tumor cells. Nature 370:61–65

    Article  PubMed  CAS  Google Scholar 

  • Seiki M (2002) The cell surface: the stage for matrix metalloproteinase regulation of migration. Curr Opin Cell Biol 14:624–632

    Article  PubMed  CAS  Google Scholar 

  • Sela-Passwell N et al (2010) Structural and functional base for allosteric control of MMP activities. Biochim Biophys Acta 1803:29–38

    Article  CAS  Google Scholar 

  • Sparano JA et al (2004) Randomized phase III trial of marimastat versus placebo in patients with metastatic breast cancer who have responding or stable disease after first-line chemotherapy: An Eastern Cooperative Oncology Group trial (E2196). J Clin Oncol 22:4631–4638

    Google Scholar 

  • Sternlicht MD, Werb Z (2001) How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol 17:463–516

    Article  PubMed  CAS  Google Scholar 

  • Still K et al (2000) Localization and quantification of mRNA for matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) in human benign and malignant prostatic tissue. Prostate 42:18–25

    Article  PubMed  CAS  Google Scholar 

  • Stoker W, Bode W (1995) Structural features of a superfamily of zinc-endopeptidases: the metzincins. Curr Opin Struct Biol 5:383–390

    Article  Google Scholar 

  • Strongin AY et al (1995) Mechanism of cell surface activation of 72-kDa type IV collagenase. Isolation of the activated form of the membrane metalloproteinase. J Biol Chem 270:5331–5338

    Article  PubMed  CAS  Google Scholar 

  • Suenaga N et al (2004) CD44 binding through the hemopexin-like domain is critical for its shedding by membrane-type 1 matrix metalloproteinase. Oncogene 1–10

    Google Scholar 

  • Szabova L et al (2008) MT1-MMP is required for efficient tumor dissemination in experimental metastatic disease. Oncogene 27:3274–3281

    Article  PubMed  CAS  Google Scholar 

  • Takahashi C et al (1998) Regulation of matrix metalloproteinase-9 and inhibition of tumor invasion by the membrane-anchored glycoprotein RECK. Proc Natl Acad Sci U S A 95:13221–13226

    Article  PubMed  CAS  Google Scholar 

  • Tallant C, Marrero A, Gomis-Ruth FX (2010) Matrix metalloproteinases: fold and function of their catalytic domains. Biochim Biophys Acta 1803:20–28

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Thiolloy S et al (2009) Osteoclast-derived matrix metalloproteinase-7, but not matrix metalloproteinase-9, contributes to tumor-induced osteolysis. Cancer Res 69:6747–6755

    Article  PubMed  CAS  Google Scholar 

  • Thompson EW, Newgreen DF (2005) Carcinoma invasion and metastasis: a role for epithelial–mesenchymal transition? Cancer Res 65:5991–6001

    Article  PubMed  CAS  Google Scholar 

  • Vargo-Gogola T et al (2002) Matrilysin (matrix metalloproteinase-7) selects for apoptosis-resistant mammary cells in vivo. Cancer Res 62:5559–5563

    PubMed  CAS  Google Scholar 

  • Vincenti MP, Brinkerhoff CE (2007) Signal transduction and cell-type specific regulation of matrix metalloproteinase gene expression: can MMPs be good for you? J Cell Physiol 213:355–363

    Article  PubMed  CAS  Google Scholar 

  • Wang W, Eddy R, Condeelis J (2007) The cofilin pathway in breast cancer invasion. Nat Rev 7:429–440

    CAS  Google Scholar 

  • Wolf K et al (2003) Compensation mechanism in tumor cell migration: mesenchymal-amoeboid transition after blocking of pericellular proteolysis. J Cell Biol 160:267–277

    Article  PubMed  CAS  Google Scholar 

  • Wolf K et al (2007) Multi-step pericellular proteolysis controls the transition from individual to collective cancer cell invasion. Nat Cell Biol 9:893–904

    Article  PubMed  CAS  Google Scholar 

  • Xu J et al (2001) Proteolytic exposure of a cryptic site within collagen type IV is required for angiogenesis and tumor growth in vivo. J Cell Biol 154:1069–1079

    Article  PubMed  CAS  Google Scholar 

  • Yamada KM, Cukierman E (2007) Modeling tissue morphogenesis and cancer in 3D. Cell 130:601–610

    Article  PubMed  CAS  Google Scholar 

  • Yamagucki H, Wyckoff J, Condeelis J (2005) Cell migration in tumors. Curr Opin Cell Biol 17:559–564

    Article  CAS  Google Scholar 

  • Yan C, Wang H, Boyd DD (2001) KiSS-1 represses 92-kDa type IV collagenase expression by down-regulating NFkB binding to the promoter as a consequence of Ik B alpha induced block of p65/p50 nuclear translocation. J Biol Chem 276:1162–1172

    Google Scholar 

  • Yang J et al (2004) Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117:927–939

    Article  PubMed  CAS  Google Scholar 

  • Yang W et al (2001) Human macrophage metalloelastase gene expression in colorectal carcinoma and its clinicopathologic significance. Cancer 91:1277–1283

    Article  PubMed  CAS  Google Scholar 

  • Yu Q, Stamenkovic I (1999) Localization of matrix metalloproteinase 9 to the cell surface provides a mechanism for CD44-mediated tumor invasion. Genes Dev 13:35–48

    Article  PubMed  CAS  Google Scholar 

  • Zi X et al (2005) Expression of Frzb/secreted frizzled-related protein 3, a secreted Wnt antagonist, in human androgen-independent prostate cancer PC-3 cells suppresses tumor growth and cellular invasion. Cancer Res 65:9762–9770

    Article  PubMed  CAS  Google Scholar 

  • Zucker S, Cao J, Chen W-T (2001a) Critical appraisal of the use of matrix metalloproteinase inhibitors in cancer treatment. Oncogene 19:6642–6650

    Article  CAS  Google Scholar 

  • Zucker S et al (2001b) Tumorigenic potential of extracellular matrix metalloproteinase induce (EMMPRIN). Am J Pathol 158:1921–1928

    Article  PubMed  CAS  Google Scholar 

  • Zucker S, Cao J, Molloy CJ (2002) Role of matrix metalloproteinases and plasminogen activators in cancer and metastasis. Therapeutic strategies. In: Baguley BC, Kerr DJ (eds) Anticancer drug development. Academic, San Diego, CA, pp 91–122

    Chapter  Google Scholar 

  • Zucker S et al (1995) Thrombin induces the activation of progelatinase A in vascular endothelial cells: Physiologic regulation of angiogenesis. J Biol Chem 270:23730–23738

    Article  PubMed  CAS  Google Scholar 

  • Zucker S, Doshi K, Cao J (2004a) Measurement of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMP) in blood and urine: potential clinical applications. Adv Clin Chem 38:37–85

    Article  PubMed  CAS  Google Scholar 

  • Zucker S et al (2004b) TIMP-2 is released as an intact molecule following binding to MT1-MMP on the cell surface. Exp Cell Res 293:164–174

    Article  PubMed  CAS  Google Scholar 

  • Zucker S et al (1985) Diversity of melanoma plasma membrane proteinases. Inhibition of collagenolysis and cytolytic activity by minocycline. J Natl Cancer Inst 75:517–525

    PubMed  CAS  Google Scholar 

  • Zucker S et al (1992) Type IV collagenase/gelatinase (MMP2) is not increased in plasma of patients with cancer. Cancer Epidemiol Biomarkers Prev 1:475–479

    PubMed  CAS  Google Scholar 

  • Zucker S et al (1998) Vascular endothelial growth factor and matrix metalloproteinase production in endothelial cells: conversion of prothrombin to thrombin results in progelatinase A activation and cell proliferation. Int J Cancer 75:780–786

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work support was provided by a Merit Review Grant from the Department of Veterans Affairs, NIH grant (RO1 CA11355301A1), a Baldwin Breast Cancer Foundation grant and a Walk-for-Beauty grant from the Research Foundation, Stony Brook University.

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  1. Veterans Affairs Medical Center, Northport, NY, 11768, USA

    Stanley Zucker

  2. Stony Brook University, Stony Brook, NY, 11794, USA

    Stanley Zucker

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Correspondence to Stanley Zucker .

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    Rebecca G. Bagley

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Zucker, S., Cao, J. (2010). Matrix Metalloproteinases and Cancer Cell Invasion/Metastasis. In: Bagley, R. (eds) The Tumor Microenvironment. Cancer Drug Discovery and Development. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6615-5_25

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