Abstract
Membrane-type MMPs (MT-MMPs) constitute a growing subclass of recently identified matrix metalloproteinases (MMPs). In addition to the highly conserved MMP functional domains, the MT-MMPs have additional insertion sequences (IS) that confer unique functional roles. While most of the MMPs are secreted, the MT-MMPs are membrane associated and a number of these have cytoplasmic domains which may be important in cellular signaling. This membrane localization leads to focal areas of receptor recruitment and subsequent activity, thereby enhancing pericellular proteolysis in specific areas of contact within the brain interstitium. MT1-MMP is the best-characterized MT-MMP, the measure against which subsequently cloned homologues are compared. MT1-MMP activates proMMP2 via its interaction with TIMP2, which serves as an intermolecular bridge for proMMP2 binding to MT-MMPs. In addition to activation of proMMP2, MT-MMPs display intrinsic proteolytic activity towards extracellular matrix molecules (ECM), which is independent of MMP2 activation. The increased expression levels of several members of the MMP family have been shown to correlate with high-grade gliomas, including MT1-MMP. Despite improvements in the diagnosis and treatment of patients with glial tumors, they remain the most common and least curable brain cancer in adults. The ability of glioma cells to infiltrate surrounding brain tissue, and ultimately escape current therapeutic modalities, could potentially be minimized using anti-invasive therapies. Proteolysis is a necessary part of the invasion process, within which the MT-MMPs appear to play a central role. The development of pharmaceutical approaches that target expression and regulation of MT-MMPs may prove beneficial in targeting invading glioma cells.
Similar content being viewed by others
References
Chintala SK, Tonn JC, Rao JS: Matrix metalloproteinases and their biological function in human gliomas. Int J Dev Neurosci 17(5–6): 495–502, 1999
Jones JL, Walker RA: Control of matrix metalloproteinase activity in cancer. J Pathol 183: 377–379, 1997
Frosch BA, Sloane BF: The role of proteolytic enzymes in brain tumor infiltration. In: Mikkelsen T, Bjerkvig R, Laerum OD, Rosenblum ML (eds) Brain Tumor Invasion: Biological, Clinical and Therapeutic Considerations, John Wiley & Sons Inc. 1998, pp 275–300
Nakagawa T, Kubota T, Kabuto M, Fujimoto N, Okada Y: Secretion of matrix metalloproteinase-2 (72 kDa gelatinase/ Type IV collagenase = gelatinase A) by malignant human glioma cell lines: implications for the growth and cellular invasion of the extracellular matrix. J Neuro-Oncol 28(1): 13–24, 1996
Tonn JC, Kerkau S, Hanke A, Bouterfa H, Mueller JG, Wagner S, Vince GH, Roosen K: Effect of synthetic matrixmetalloproteinase inhibitors on invasive capacity and proliferation of human malignant gliomas in vitro. Int J Cancer 80(5): 764–772, 1999
Deryugina EI, Bourdon MA, Luo G-X, Reisfeld RA, Strongin A: Matrix metalloproteinase-2 activation modulates glioma cell migration. J Cell Science 110: 2473–2482, 1997
Goldbrunner RH, Bernstein JJ, Tonn JC: Cell-extracellular matrix interaction in glioma invasion. Acta Neurochir (Wien) 141(3): 295–305, 1999
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 metallo-proteinases in human astrocytic tumors. Amer J Pathol 154(2): 417–428, 1999
Uhm JH, Dooley NP, Villemure JG, Yong VW: Glioma invasion in vitro: regulation by matrix metalloprotease-2 and protein kinase C. Clin Exp Metastasis 14(5): 421–433, 1996
Yamamoto M, Mohanam S, Sawaya R, Fuller GN, Seiki M, Sato H, Godaslan 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
Nakano A, Tani E, Miyazakai K, Yamamoto Y, Furuyama JI: Matrix metallo-proteinases and tissue inhibitors of metalloproteinases in human gliomas. J Neurosurg 83: 298–307, 1995
Halaka AN, Bunning RAD, Bird CC, Gibson M, Reynolds JJ: Production of collagenase and inhibitor (TIMP) by intracranial tumors and dura in vitro. J Neurosurg 59: 461–466, 1983
Uhm JH, Dooley NP, Villemure JG, Yong VW: Mechanisms of glioma invasion: role of matrix-metalloproteinases. Can J Neurol Sci 24: 3–15, 1997
Kruger A, Sanchez-Sweatman OH, Martin DC, Fata JE, Ho AT, Orr FW, Ruther U, Khokha R: Host TIMP-1 expression confers resistance to experimental brain metastasis of a fibrosarcoma cell line. Oncogene 61: 1272–1275, 2001
Itoh T, Tanioka M, Yoshida H, Yoshioka T, Nishimoto H, Itohara S: Reduced angiogenesis and tumor progression in gelatinase A deficient mice. Cancer Res 58: 1048–1051, 1998
Vince GH, Wagner S, Pietsch T, Klein R, Goldbrunner RH, Roosen K, Tonn JC: Heterogeneous regional expression patterns of matrix metalloproteinases in human malignant gliomas. Int J Dev Neurosci 17(5–6): 437–445, 1999
Nagase H, Woessner JF: Matrix metalloproteinases. J Biol Chem 274(31): 21491–21494, 1999
Yana I, Weiss SJ: Regulation of membrane type-1 matrix metalloproteinase activation by proprotein convertases. Mol Biol Cell 11(7): 2387–2401, 2000
Itoh Y, Kajita M, Kinoh H, Mori H, Okada A, Seiki M: Membrane type 4 matrix metalloproteinase (MT4-MMP, MMP-17) is a glycosylphosphatidylinositol-anchored proteinase. J Biol Chem 274(48): 34260–34266, 1999
Kojima S, Itoh Y, Matsumoto S, Masuho Y, Seiki M: Membrane-type 6 matrix metalloproteinase (MT6-MMP, MMP-25) is the second glycosyl-phosphatidyl inositol (GPI)-anchoredMMP. FEBS Lett 480(2–3): 142–146, 2000
Sato H, Takino T, Okada Y, Cao J, Shinagawa A, Yamamoto E, Seiki M: A matrix metalloproteinase expressed on the surface of invasive tumour cells. Nature 370(6484): 61–65, 1994
Okada A, Bellocq JP, Rouyer N, Chenard MP, Rio MC, Chambon P, Basset P: Membrane-type matrix metalloproteinase (MT-MMP) gene is expressed in stromal cells of human colon, breast, and head and neck carcinomas. Proc Natl Acad Sci USA 92(7): 2730–2734, 1995
Will H, Hinzmann B: cDNA sequence and mRNA tissue distribution of a novel human matrix metalloproteinase with a potential transmembrane segment. Europ J Biochem 231: 602–608,1995
Takino T, Sato H, Shinagawa A, Seiki M: Identification of the second membrane-type matrix metalloproteinase (MT-MMP-2) gene from a placenta cDNA library. MT-MMPs form a unique membrane-type subclass in the MMP family. J Biol Chem 270(39): 23013–23020, 1995
Matsumoto S, Katoh M, Saito S, Watanabe T, Masuho Y: Identification of soluble type of membrane-type matrix metalloproteinase-3 formed by alternatively splicedmRNA. Biochim Biophys Acta 1354(2): 159–170, 1997
Puente XS, Pendas AM, Llano E, Velasco G, Lopez-Otin C: Molecular cloning of a novel membrane-type matrix metalloproteinase from a human breast carcinoma. Cancer Res 56(5): 944–949, 1996
Kajita M, Kinoh H, Ito N, Takamura A, Itoh Y, Okada A, Sato H, Seiki M: Human membrane type-4 matrix metalloproteinase (MT4-MMP) is encoded by a novel major transcript: isolation of complementary DNA clones for human and mouse MT4-MMP transcripts. FEBS Lett 457(3): 353–356, 1999
Llano E, Pendas AM, Freije JP, Nakano A, Knauper V, Murphy G, Lopez-Otin C: Identification and characterisation of humanMT5-MMP, a newmembrane-bound activator of progelatinase A over-expressed in brain tumors. Cancer Res 59: 2570–2576, 1999
Pei D: Leukolysin/MMP25/MT6-MMP: a novel matrix metalloproteinase specifically expressed in the leukocyte lineage. Cell Res 9(4): 291–303, 1999
Velasco G, Cal S, Merlos-Suarez A, Ferrando AA, Alvarez S, Nakano A, Arribas J, Lopez-Otin C: Human MT6-matrix metalloproteinase: identification, progelatinase A activation, and expression in brain tumors. Cancer Res 60(4): 877–882, 2000
Bernot A, Heilig R, Clepet C, Smaoui N, Da Silva C, Petit JL, Devaud C, Chiannilkulchai N, Fizames C, Samson D, Cruaud C, Caloustian C, Gyapay G, Delpech M, Weissenbach J: A transcriptional map of the FMF region. Genomics 50(2): 147–160, 1998
Imai K, Ohuchi E, Aoki T, Nomura H, Fujii Y, Sato H, Seiki M, Okada Y: Membrane-type matrix metalloproteinase 1 is a gelatinolytic enzyme and is secreted in a complex with tissue inhibitor of metalloproteinases 2. Cancer Res 56(12): 2707–2710, 1996
Cao J, Rehemtulla A, Bahou W, Zucker S: Membrane type matrix metalloproteinase activates pro-gelatinase A without furin cleavage of the N-terminal domain. J Biol Chem 271(47): 30174–30180, 1996
Cao J, Hymowitz M, Conner C, Bahou WF, Zucker S: The propeptide domain of membrane type 1-matrix metalloproteinase acts as an intramolecular chaperone when expressed in trans with the mature sequence inCOS1cells. J BiolChem 275(38): 29648–29653, 2000
Sato T, Kondo T, Fujisawa T, Seiki M, Ito A: Furin-independent pathway of membrane type 1-matrix metalloproteinase activation in rabbit dermal fibroblasts. J Biol Chem 274(52): 37280–37284, 1999
Romanic AM, Madri JA: Extracellular matrix-degrading proteinases in the nervous system. Brain Pathol 4: 145–156, 1994
D'Ortho MP, Will H, Atkinson S, Butler G, Messent A, Gavrilovic J, Smith B, Timpl R, Zardi L, Murphy G: Membrane-type matrix metalloproteinases 1 and 2 (MT1-MMP and MT2-MMP) exhibit a broad spectrum proteolytic capacity comparable to many matrix metalloproteinases. Eur J Biochem 250: 51–57, 1997
Butler GS, Will H, Atkinson SJ, Murphy G: Membranetype-2 matrix metalloproteinase can initiate the processing of progelatinaseAand is regulated by the tissue inhibitors of metalloproteinases. Eur J Biochem 244(2): 653–657, 1997
Miyamori H, Takino T, Seiki M, Sato H: Human membrane type-2 matrix metalloproteinase is defective in cellassociated activation of progelatinase A. Biochem Biophys Res Commun 267(3): 796–800, 2000
Nakahara H, Howard L, Thompson EW, Sato H, Seiki M, Yeh Y, Chen WT: Transmembrane/cytoplasmic domainmediated membrane type-1 matrix metalloproteinase docking to invadopodia is required for cell invasion. Proc Natl Acad Sci USA 94(15): 7959–7964, 1997
Urena JM, Merlos-Suarez A, Baselga J, Arribas J: The cytoplasmic carboxy-terminal amino acid determines the subcellular localization of proTGF-(alpha) and membrane type matrix metalloprotease (MT1-MMP). J Cell Sci 112 (Pt 6): 773–784, 1999
Lehti K, Valtanen H, Wickstrom S, Lohi J, Keski-Oja J: Regulation of membrane-type-1 matrix metalloproteinase activity by its cytoplasmic domain. J Biol Chem 275(20): 15006–15013, 2000
Holmbeck K, Bianco P, Caterina J, Yamada S, Kromer M, Kuznetsov SA, Mankani M, Robey PG, Poole AR, Pidoux I, Ward JM, Birkedal-Hansen H: MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover. Cell 99(1): 81–92, 1999
Zhou Z, Apte SS, Soininen R, Cao R, Baaklini GY, Rauser RW, Wang J, Cao Y, Tryggvason K: Impaired endochondral ossification and angiogenesis in mice deficient in membrane-type matrix metalloproteinase I. Proc Natl Acad Sci USA 97(8): 4052–4057, 2000
Hiraoka N, Allen E, Apel IJ, Gyetko MR, Weiss SJ: Matrix metalloproteinases regulate neovascularization by acting as pericellular fibrinolysins. Cell 95(3): 365–377, 1998
Haas TL, Davis SJ, Madri JA: Three-dimensional type I collagen lattices induce coordinate expression of matrix metalloproteinases MT1-MMP and MMP-2 in microvascular endothelial cells. J Biol Chem 273(6): 3604–3610, 1998
Murphy G, Stanton H, Cowell S, Butler G, Knauper V, Atkinson S, Gavrilovic J: Mechanisms for pro matrix metalloproteinase activation. APMIS 107(1): 38–44, 1999
Imai K, Ohuchi E, Aoki T, Nomura H, Fujii Y, Sato H, Seiki M, Okada Y: Membrane-type matrix metalloproteinase 1 is a gelatinolytic enzyme and is secreted in as complex with tissue inhibitor of metalloproteinases 2. Cancer Res 56: 2707–2710, 1998
Overall CM, Tam E, McQuibban GA, Morrison C, Wallon UM, Bigg HF, King AE, Roberts CR: Domain interactions in the gelatinase A.TIMP-2.MT1-MMP activation complex. The ectodomain of the 44-kDa form of membrane type-1 matrix metalloproteinase does not modulate gelatinaseAactivation. J Biol Chem 275(50): 39497–39506, 2000
Zucker S, Drews M, Conner C, Foda HD, DeClerck YA, Langley KE, Bahou WF, Docherty AJ, Cao J: Tissue inhibitor of metalloproteinase-2 (TIMP-2) binds to the catalytic domain of the cell surface receptor, membrane type-1 matrix metalloproteinase 1 (MT1-MMP). J Biol Chem 273(2): 1216–1222, 1998
Toth M, Bernardo MM, Gervasi DC, Soloway PD, Wang Z, Bigg HF, Overall CM, DeClerck YA, Tschesche H, Cher ML, Brown S, Mobashery S, Fridman R: Tissue inhibitor of metalloproteinase (TIMP)-2 acts synergistically with synthetic matrix metalloproteinase (MMP) inhibitors but not with TIMP-4 to enhance the (Membrane type 1)-MMP-dependent activation of proMMP-2. J Biol Chem 275(52): 41415–41423, 2000
Wang Z, Juttermann R, Soloway PD: TIMP-2 is required for efficient activation of proMMP-2 in vivo. J Biol Chem 275(34): 26411–26415, 2000
Hernandez-Barrantes S, Toth M, Bernardo MM, Yurkova M, Gervasi DC, Raz Y, Sang QA, Fridman R: Binding of active (57 kDa) membrane type 1-matrix metalloproteinase (MT1-MMP) to tissue nhibitor of metalloproteinase (TIMP)-2 regulates MT1-MMP processing and proMMP-2 activation. J Biol Chem 275(16): 12080–12089, 2000
Maquoi E, Frankenne F, Baramova E, Munaut C, Sounni NE, Remacle A, Noel A, Murphy G, Foidart JM: Membrane type 1 matrix metalloproteinase-associated degradation of tissue inhibitor of metalloproteinase 2 in human tumor cell lines. J Biol Chem 275(15): 11368–11378, 2000
Pei D, Weiss SJ: Transmembrane-deletion mutants of the membrane-type matrix metalloproteinase-1 process progelatinase A and express intrinsic matrix-degrading activity. J Biol Chem 271(15): 9135–9140, 1996
Ohuchi E, Imai K, Fujii Y, Sato H, Seiki M, Okada Y: Membrane type 1 matrix metalloproteinase digests interstitial collagens and other extracellular matrix macromolecules. J Biol Chem 272(4): 2446–2451, 1997
Giese A, Westphal M:Glioma invasion in the central nervous system. Neurosurg 39: 235–252, 1996
English WR, Puente XS, Freije JM, Knauper V, Amour A, Merryweather A, Lopez-Otin C, Murphy G: Membrane type 4 matrix metalloproteinase (MMP17) has tumor necrosis factor-alpha convertase activity but does not activate proMMP2. J Biol Chem 275(19): 14046–14055, 2000
Hotary K, Allen E, Punturieri A, Yana I, Weiss SJ: Regulation of cell invasion and morphogenesis in a threedimensional type I collagen matrix by membrane-type matrix metalloproteinases 1, 2, and 3. J Cell Biol 149(6): 1309–1323, 2000
Brooks PC, Stromblad S, Sanders LC, von Schalscha TL, Aimes RT, Stetler-Stevenson WG, Quigley JP, Cheresh DA: Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3. Cell 85(5): 683–693, 1996
Han YP, Tuan TL, Wu H, Hughes M, Garner WL: TNF-α stimulates activation of proMMP2 in human skin through NF-κB mediated induction of MT1-MMP. J Cell Sci 114(Pt 1): 131–139, 2001
Lohi J, Lehti K, Westermarck J, Kahari V, Keski-Oja J: Regulation of membrane-type matrix metalloproteinae-1 expression by growth factors and phorbol 12-myristate 13-acetate. FEBS 239: 239–247, 1996
Tomasek JJ, Halliday NL, Updike DL, Ahern-Moore JS, Vu TK, Liu RW, Howard EW: Gelatinase A activation is regulated by the organization of the polymerized actin cytoskeleton. J Biol Chem 272(11):7482–7487, 1997
Lohi J, Lehti K, Valtanen H, Parks WC, Keski-Oja J: Structural analysis and promoter characterization of the human membrane-type matrix metalloproteinase-1 (MT1-MMP) gene. Gene 242(1–2): 75–86, 2000
Sameshima T, Nabeshima K, Toole BP, Yokogami K, Okada Y, Goya T, Koono M, Wakisaka S: Glioma cell extracellular matrix metalloproteinase inducer(EMMPRIN) (CD147) stimulates production of membrane-type matrix metalloproteinases and activated gelatinase A in co-cultures with brain-derived fibroblasts. Cancer Lett 157(2): 177–184, 2000
Hamasuna R, Kataoka H, Moriyama T, Itoh H, Seiki M, Koono M: Regulation of matrix metalloproteinase-2 (MMP-2) by hepatocyte growth factor/scatter factor (HGF/SF) in human glioma cells: HGF/SF enhances MMP-2 expression and activation accompanying upregulation of membrane type-1 MMP. Int J Cancer 82(2): 274–281, 1999
Park MJ, Park IC, Hur JH, Rhee CH, Choe TB, Yi DH, Hong SI, Lee SH: Protein kinase C activation by phorbol ester increases in vitro invasion through regulation of matrix metalloproteinases/tissue inhibitors of metalloproteinases system in D54 human glioblastoma cells. Neurosci Lett 290(3): 201–204, 2000
Deb S, Zhang JW, Gottschall PE: Activated isoforms of MMP-2 are induced in U87 human glioma cells in response to beta-amyloid peptide. J Neurosci Res 55(1): 44–53, 1999
Lukes A, Mun-Bryce S, Lukes M, Rosenberg GA: Extracellular matrix degradation by metalloproteinases and central nervous system diseases. Mol Neurobiol 19(3): 267–284, 1999
Vu TH, Werb Z: Matrix metalloproteinases: effectors of development and normal physiology. Genes Dev 14(17): 2123–2133, 2000
Polette M, Birembaut P: Membrane-type metalloproteinases in tumor invasion. Int J Biochem Cell Biol 30(11): 1195–1202, 1998
Hur JH, Park MJ, Park IC, Yi DH, Rhee CH, Hong SI, Lee SH: Matrix metalloproteinases in human gliomas: activation of matrix metalloproteinase-2 (MMP-2) may be correlated with membrane-type-1 matrix metalloproteinase (MT1-MMP) expression. JKorean Med Sci 15(3): 309–314, 2000
Giambernardi TA, Grant GM, Taylor GP, Hay RJ, Maher VM, McCormick JJ, Klebe RJ: Overview of matrix metalloproteinase expression in cultured cells. Matrix Biol 16: 483–496, 1998
Shofuda K-I, Moriyama K, Nishibashi A, Higashi S, Mizushima H, Yasumitsu H, Miki K, Sato H, Seiki M, Miyazaki K: Role of tissue inhibitor of metalloproteinases-2 (TIMP-2) in regulation of pro-gelatinase A activation catalyzed by membrane-type matrix metalloproteinase-1 (MT1-MMP) in human cancer cells. J Biochem 124: 462–470, 1998
Lampert K, Machein U, Machein MR, Conca W, Peter HH, Volk B: Expression of matrix metalloproteinases and their tissue inhibitors in human brain tumors.AmJ Pathol 153(2): 429–437, 1998
Tews DS, Nissen A: Expression of adhesion factors and degrading proteins in primary and secondary glioblastomas and their precursor tumors. Invasion Metastasis 18(5–6): 271–284, 1998–1999
Rooprai HK, Van Meter T, Rucklidge GJ, Hudson L, Everall IP, Pilkington GJ: Comparative analysis of matrix metalloproteinases by immunocytochemistry, immunohistochemistry and zymography in human primary brain tumours. Int J Oncol 13(6): 153–157, 1998
Forsyth PA, Wong H, Laing TD, Rewcastle NB, Morris DG, Muzik H, Leco KJ, Johnston RN, Brasher PMA, Sutherland G, Edwards DR: Gelatinase-A (MMP-2), gelatinase-B (MMP-9), and membrane type matrix metalloproteinase-1 (MT1-MMP) are involved in different aspects of the pathophysiology of malignant gliomas. J Cancer 79: 1828–1835, 1999
Belien AT, Paganetti PA, Schwab ME: Membrane-type 1 matrix metalloprotease (MT1-MMP) enables invasive migration of glioma cells in central nervous system white matter. J Cell Biol 144(2): 373–384, 1999
Kruger A, Soeltl R, Sopov I, Kopitz C, Arlt M, Magdolen V, Harbeck N, Gansbacher B, Schmitt M: Hydroxamate-type matrix metallooproteinase inhibitor batimastat promotes liver metastases. Cancer Res 61: 1272–1275, 2001
Hynes RO. Cell adhesion: old and new questions. TIBS 24(12): M33–7, 1999
Bein K, Simons M: Thrombospondin type 1 repeats interact with matrix metalloproteinase 2. Regulation of metalloproteinase activity. J Biol Chem 275(41): 32167–32173, 2000
Yong VW, Krekoski CA, Forsyth PA, Bell R, Edwards DR: Matrix metallo-proteinases and diseases of the CNS. Trends Neurosci 21(2): 75–80, 1998
Rathke-Hartlieb S, Budde P, Ewert S, Schlomann U, Staege MS, Jockusch H, Bartsch JW, Frey J: Elevated expression of membrane type 1 metalloproteinase (MT1-MMP) in reactive astrocytes following neurodegeneration in mouse central nervous system. FEBS Lett 481(3): 227–234, 2000
Yoshiyama Y, Sato H, Seiki M, Shinagawa A, Takahashi M, Yamada T: Expression of the membrane-type 3 matrix metalloproteinase (MT3-MMP) in human brain tissues. Acta Neuropathol (Berl) 96(4): 347–350, 1998
Jaworski DM: Developmental regulation of membrane type-5 matrix metalloproteinase (MT5-MMP) expression in the rat nervous system. Brain Res 860(1–2): 174–177, 2000
Itoh Y, Kajita M, Kinoh H, Mori H, Okada A, Seiki M: Membrane type 4 matrix metalloproteinase (MT4-MMP, MMP-17) is a glycosylphosphatidylinositolanchored proteinase. J Biol Chem 274(48): 34260–34266, 1999
Mattei MG, Roeckel N, Olsen BR, Apte SS: Genes of the membrane-type matrix metalloproteinase (MT-MMP) gene family, MMP14, MMP15, and MMP16, localize to human chromosomes 14, 16, and 8, respectively. Genomics 40(1): 168–169, 1997
Puente XS, Pendas AM, Llano E, Lopez-Otin C: Localization of the human membrane type 4-matrix metalloproteinase gene (MMP17) to chromosome 12q24. Genomics 54(3): 578–579, 1998
Rutka JT, Matsuzawa K, Hubbard SL, Fukuyama K, Becker L, Stetler-Stevenson W, Edwards D, Dirks PB: Expression of TIMP-1, TIMP-2, 72-and 92-kDa type IV collagenase transcripts in human astrocytoma cell lines: correlation with invasiveness. Int J Oncol 6: 877–884, 1995
Murphy G, Gavrilovic J: Proteolysis and cell migration: creating a path? Curr Op Biol 11: 614–621, 1999
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Fillmore, H.L., VanMeter, T.E. & Broaddus, W.C. Membrane-type Matrix Metalloproteinases (MT-MMP)s: Expression and Function During Glioma Invasion. J Neurooncol 53, 187–202 (2001). https://doi.org/10.1023/A:1012213604731
Issue Date:
DOI: https://doi.org/10.1023/A:1012213604731