Abstract
Previous experimental and biochemical studies on matrix metalloproteinases (MMPs) have indicated that MMPs are implicated in cancer invasion and metastases. Studies on the expression of MMPs and tissue inhibitors of metalloproteinases (TIMPs) in various human cancer tissues have further demonstrated that activation of proMMP-2 mediated by a combination of TIMP-2 and MT1-MMP (the proMMP-2/TIMP-2/MT1-MMP system) correlates well with the progression of most of these cancers such as the breast carcinomas, thyroid papillary carcinomas, gastric adenocarcinomas, oral squamous cell carcinomas and gliomas, whereas MMP-7 plays an important role in the metastases of endometrial and gastrointestinal carcinomas. Although MMP-7 is a typical secreted MMP, a member of transmembrane 4 superfamily (TM4SF) captures proMMP-7 on the carcinoma cell membranes through interaction with its propeptide, leading to its pericellular activation. Thus, these results strongly suggest that proteolysis at the cell-extracellular matrix interfaces of cancer cells by the proMMP-2/TIMP-2/MT1-MMP and proMMP-7/TM4SF systems plays crucial roles in the progression of human cancers. In this article, we address the current views on the roles of these MMPs acting on the cell membranes in human cancer invasion and metastases.
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References
Sternlicht MD, Werb Z: How matrixmetalloprot einases regulate cell behavior. Annu Rev Cell Dev Biol 17: 463–516, 2001
Egeblad M, Werb Z: New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2: 161–174, 2002
Ueno H, Nakamura H, Inoue M, Imai K, Noguchi M, Sato H, Seiki M, Okada Y: Expression and tissue localization of membrane-types 1, 2, and 3 matrixmetallopro teinases in human invasive breast carcinomas. Cancer Res 57: 2055–2060, 1997
Nakamura H, Ueno H, Yamashita K, Shimada T, Yamamoto E, Noguchi M, Fujimoto N, Sato H, Seiki M, Okada Y: Enhanced production and activation of progelatinase A mediated by membrane-type 1 matrixmetalloproteinase in human papillary thyroid carcinomas. Cancer Res 59: 467–473, 1999
Ueno H, Yamashita K, Azumano I, Inoue M, Okada Y: Enhanced production and activation of matrixmetalloproteinase-7 (matrilysin) in human endometrial carcinomas. Int J Cancer 84: 470–477, 1999
Nomura H, Sato H, Seiki M, Mai M, Okada Y: Expression of membrane-type matrix metalloproteinase in human gastric carcinomas. Cancer Res 55: 3263–3266, 1995
Nomura H, Fujimoto N, Seiki M, Mai M, Okada Y: Enhanced production of matrixmetalloproteinases and activation of matrixmetallo proteinase 2 (gelatinase A) in human gastric carcinomas. Int J Cancer 69: 9–16, 1996
Yamashita K, Azumano I, Mai M, Okada Y: Expression and tissue localization of matrixmetallo proteinase 7 (matrilysin) in human gastric carcinomas. Implications for vessel invasion and metastasis. Int J Cancer 79: 187–194, 1998
Shimada T, Nakamura H, Yamashita K, Kawata R, Murakami Y, Fujimoto N, Sato H, Seiki M, Okada Y: Enhanced production and activation of progelatinase A mediated by membrane-type 1 matrixmetalloprotein ase in human oral squamous cell carcinomas: Implications for lymph node metastasis. Clin Exp Metastasis 18: 179–188, 2000
Nakada M, Nakamura H, Ikeda E, Fujimoto N, Yamashita J, Sato H, Seiki M, Okada Y: Expression and tissue localization of membrane-type 1, 2, and 3 matrixmetalloproteinases in human astrocytic tumors. Am J Pathol 154: 417–428, 1999
Nakada M, Kita D, Futami K, Yamashita J, Fujimoto N, Sato H, Okada Y: Roles of membrane type 1 matrix metalloproteinase and tissue inhibitor of metalloproteinases 2 in invasion and dissemination of human malignant glioma. J Neurosurg 94: 464–473, 2001
Fujimoto N, Iwata K: Use of EIA to measure MMPs and TIMPs. In: Clark IM (ed.) MatrixMetallop roteinase Protocols. Humana Press Inc., Totowa, 2001, pp 347–358
Liotta LA, Tryggvason K, Garbisa S, Hart I, Foltz CM, Shafie S: Metastatic potential correlates with enzymatic degradation of basement membrane collagen. Nature 284: 67–68, 1980
Okada Y: Proteinases and matrixdegradation. In: Ruddy S, Harris ED, Jr, Sledge CB (eds.) (6th edition) Kelly's textbook of rheumatology. W.B. Saunders Company, Philadelphia, 2001, 55–72
Hua J, Muschel RJ: Inhibition of matrixmetallo proteinase 9 expression by a ribozyme blocks metastasis in a rat sarcoma model system. Cancer Res 56: 5279–5284, 1996
Brown PD, Bloxidge RE, Anderson E, Howell A: Expression of activated gelatinase in human invasive breast carcinoma. Clin Exp Metastasis 11: 183–189, 1993
Brown PD, Bloxidge RE, Stuart NS, Gatter KC, Carmichael J: Association between expression of activated 72-kilodalton gelatinase and tumor spread in non-small-cell lung carcinoma. J Natl Cancer Inst 85: 574–578, 1993
Tokuraku M, Sato H, Murakami S, Okada Y, Watanabe Y, Seiki M: Activation of the precursor of gelatinase A/72 kDa type IV collagenase/MMP-2 in lung carcinomas correlates with the expression of membrane-type matrix metalloproteinase (MT-MMP) and with lymph node metastasis. Int J Cancer 64: 355–359, 1995
Sato H, Takino T, Okada Y, Cao J, Shinagawa A, Yamamoto E, Seiki M: A matrixmetallo proteinase expressed on the surface of invasive tumor cells. Nature 370: 61–65, 1994
Tsunezuka Y, Kinoh H, Takino T, Watanabe Y, Okada Y, Shinagawa A, Sato H, Seiki M: Expression of membrane-type matrixmetalloprotein ase 1 (MT1-MMP) in tumor cells enhances pulmonary metastasis in an experimental metastasis assay. Cancer Res 56: 5678–5683, 1996
Sato H, Seiki M: Membrane-type matrixmetalloprotein-ases (MT-MMPs) in tumor metastasis. J Biochem (Tokyo) 119: 209–215, 1996
Butler GS, Will H, Atkinson SJ, Murphy G: Membranetype-2 matrixmetalloprot einase can initiate the processing of progelatinase A and is regulated by the tissue inhibitors of metalloproteinases. Eur J Biochem 244: 653–657, 1997
Kinoshita T, Sato H, Okada A, Ohuchi E, Imai K, Okada Y, Seiki M: TIMP-2 promotes activation of progelatinase A by membrane-type 1 matrixmetalloprot einase immobilized on agarose beads. J Biol Chem 273: 16098–16103, 1998
Butler GS, Butler MJ, Atkinson SJ, Will H, Tamura T, van Westrum SS, Crabbe T, Clements J, d'Ortho MP, Murphy G: The TIMP2 membrane type 1 metalloproteinase “receptor” regulates the concentration and efficient activation of progelatinase A. A kinetic study. J Biol Chem 273: 871–880, 1998
Shimada T, Nakamura H, Ohuchi E, Fujii Y, Murakami Y, Sato H, Seiki M, Okada Y: Characterization of a truncated recombinant form of human membrane type 3 matrixmetalloprotein ase. Eur J Biochem 262: 907–914, 1999
Mannello F, Gazzanelli G: Tissue inhibitors of metalloproteinases and programd cell death: Conundrums, controversies and potential implications. Apoptosis 6: 479–482, 2001
Ohuchi E, Imai K, Fujii Y, Sato H, Seiki M, Okada Y: aMembrane type 1 matrixmetallopro teinase digests inter-MT1-MMP and MMP-7 in invasion and metastasis of human cancers 151 stitial collagens and other extracellular matrix macromolecules. J Biol Chem 272: 2446–2451, 1997
Lampert K, Machein U, Machein MR, Conca W, Peter HH, Volk B: Expression of matrix metalloproteinases and their tissue inhibitors in human brain tumors. Am J Pathol 153: 429–437, 1998
Yamamoto M, Mohanam S, Sawaya R, Fuller GN, Seiki M, Sato H, Gokaslan ZL, Liotta LA, Nicolson GL, Rao JS: Differential expression of membrane-type matrix metalloproteinase and its correlation with gelatinase A activation in human malignant brain tumors in vivo and in vitro. Cancer Res 56: 384–392, 1996
Forsyth PA, Wong H, Laing TD, Rewcastle NB, Morris DG, Muzik H, Leco KJ, Johnston RN, Brasher PM, Sutherland G, Edwards DR: Gelatinase-A (MMP-2), gelatinase-B (MMP-9) and membrane type matrixmetalloproteinase-1 (MT1-MMP) are involved in different aspects of the pathophysiology of malignant gliomas. Br J Cancer 79: 1828–1835, 1999
Yamaguchi Y: Lecticans: Organizers of the brain extracellular matrix. Cell Mol Life Sci 57: 276–289, 2000
Nakamura H, Fujii Y, Inoki I, Sugimoto K, Tanzawa K, Matsuki H, Miura R, Yamaguchi Y, Okada Y: Brevican is degraded by matrixmetalloprot einases and aggrecanase-1 (ADAMTS4) at different sites. J Biol Chem 275: 38885–38890, 2000
Zhang H, Kelly G, Zerillo C, Jaworski DM, Hockfield S: Expression of a cleaved brain-specific extracellular matrix protein mediates glioma cell invasion In vivo. J Neurosci 18: 2370–2376, 1998
Yoshimoto M, Itoh F, Yamamoto H, Hinoda Y, Imai K, Yachi A: Expression of MMP-7(PUMP-1) mRNA in human colorectal cancers. Int J Cancer 54: 614–618, 1993
Mori M, Barnard GF, Mimori K, Ueo H, Akiyoshi T, Sugimachi K: Overexpression of matrix metalloproteinase-7 mRNA in human colon carcinomas. Cancer 75: 1516–1519, 1995
Adachi Y, Itoh F, Yamamoto H, Matsuno K, Arimura Y, Kusano M, Endoh T, Hinoda Y, Oohara M, Hosokawa M, Imai K: Matrixmetalloprot einase matrilysin (MMP-7) participates in the progression of human gastric and esophageal cancers. Int J Oncol 13: 1031–1035, 1998
Adachi Y, Yamamoto H, Itoh F, Arimura Y, Nishi M, Endo T, Imai K: Clinicopathologic and prognostic significance of matrilysin expression at the invasive front in human colorectal cancers. Int J Cancer 95: 290–294, 2001
Yamamoto H, Itoh F, Hinoda Y, Senota A, Yoshimoto M, Nakamura H, Imai K, Yachi A: Expression of matrilysin mRNA in colorectal adenomas and its induction by truncated fibronectin. Biochem Biophys Res Commun 201: 657–664, 1994
Imai K, Yokohama Y, Nakanishi I, Ohuchi E, Fujii Y, Nakai N, Okada Y: Matrixmetallopro teinase 7 (matrilysin) from human rectal carcinoma cells. Activation of the precursor, interaction with other matrixmetalloprotein-ases and enzymic properties. J Biol Chem 270: 6691–6697, 1995
Yu WH, Woessner JF, Jr, McNeish JD, Stamenkovic I: CD44 anchors the assembly of matrilysin/MMP-7 with heparin-binding epidermal growth factor precursor and ErbB4 and regulates female reproductive organ remodeling. Genes Dev 16: 307–323, 2002
Maecker HT, Todd SC, Levy S: The tetraspanin superfamily: molecular facilitators. Faseb J 11: 428–442, 1997
Woessner JF, Jr, Taplin CJ: Purification and properties of a small latent matrixmetallopro teinase of the rat uterus. J Biol Chem 263: 16918–16925, 1988
Sires UI, Griffin GL, Broekelmann TJ, Mecham RP, Murphy G, Chung AE, Welgus HG, Senior RM: Degradation of entactin by matrixmetallopro teinases. Susceptibility to matrilysin and identification of cleavage sites. J Biol Chem 268: 2069–2074, 1993
Noe V, Fingleton B, Jacobs K, Crawford HC, Vermeulen S, Steelant W, Bruyneel E, Matrisian LM, Mareel M: Release of an invasion promoter E-cadherin fragment by matrilysin and stromelysin-1. J Cell Sci 114: 111–118, 2001
Yanez-Mo M, Tejedor R, Rousselle P, Sanchez-Madrid F: Tetraspanins in intercellular adhesion of polarized epithelial cells: Spatial and functional relationship to integrins and cadherins. J Cell Sci 114: 577–587, 2001
Guo H, Li R, Zucker S, Toole BP: EMMPRIN (CD147), an inducer of matrixmetalloprot einase synthesis, also binds interstitial collagenase to the tumor cell surface. Cancer Res 60: 888–891, 2000
Brooks PC, Stromblad S, Sanders LC, von Schalscha TL, Aimes RT, Stetler-Stevenson WG, Quigley JP, Cheresh DA: Localization of matrixmetallo proteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3. Cell 85: 683–693, 1996
Puyraimond A, Fridman R, Lemesle M, Arbeille B, Menashi S: MMP-2 colocalizes with caveolae on the surface of endothelial cells. Exp Cell Res 262: 28–36, 2001
Yu Q, Stamenkovic I: Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. Genes Dev 14: 163–176, 2000
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Shiomi, T., Okada, Y. MT1-MMP and MMP-7 in invasion and metastasis of human cancers. Cancer Metastasis Rev 22, 145–152 (2003). https://doi.org/10.1023/A:1023039230052
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DOI: https://doi.org/10.1023/A:1023039230052