Journal of Neuro-Oncology

, Volume 53, Issue 2, pp 213–235

The Role of Matrix Metalloproteinase Genes in Glioma Invasion: Co-dependent and Interactive Proteolysis

  • Timothy E. VanMeter
  • Harcharan K. Rooprai
  • Mavis M. Kibble
  • Helen L. Fillmore
  • William C. Broaddus
  • Geoffrey J. Pilkington


Matrix metalloproteinases (MMPs) are cation-dependent endopeptidases which have been implicated in the malignancy of gliomas. It is thought that the MMPs play a critical role in both metastasis and angiogenesis, and that interference with proteases might therefore deter local tumor dissemination and neovascularization. However, the attempt to control tumor-associated proteolysis will rely on better definition of the normal tissue function of MMPs, an area of study still in its infancy in the central nervous system (CNS). Understanding the role of MMP-mediated proteolysis in the brain relies heavily on advances in other areas of molecular neuroscience, most notably an understanding of extracellular matrix (ECM) composition and the function of cell adhesion molecules such as integrins, which communicate knowledge of ECM composition intracellularly. Recently, protease expression and function has been shown to be strongly influenced by the functional state and signaling properties of integrins. Here we review MMP function and expression in gliomas and present examples of MMP profiling studies in glioma tissues and cell lines by RT-PCR and Western blotting. Co-expression of MMPs and certain integrins substantiates the gathering evidence of a functional intersection between the two, and inhibition studies using recombinant TIMP-1 and integrin antisera demonstrate significant inhibition of glioma invasion in vitro. Use of promising new therapeutic compounds with anti-MMP and anti-invasion effects are discussed. These data underline the importance of functional interaction of MMPs with accessory proteins such as integrins during invasion, and the need for further studies to elucidate the molecular underpinnings of this process.

glioma matrix metalloproteinases (MMPs) integrins proteolysis invasion 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Pilkington GJ: Tumour cell migration in the central nervous system. Brain Pathol 4: 157–166, 1994Google Scholar
  2. 2.
    Giese A, Westphal M: Glioma invasion in the central nervous system. Neurosurgery 39: 235–252, 1996Google Scholar
  3. 3.
    Nakano A, Tani E, Miyazaki K, Yamamoto Y, Furuyama J: Matrix metalloproteinases and tissue inhibitors of metalloproteinases in human gliomas. J Neurosurg 83(2): 298–307, 1995Google Scholar
  4. 4.
    Sivaparvathi M, Sawaya R, Wang SW, Rayford A, Yamamoto M, Liotta LA, Nicolson GL, Rao JS: Overexpression and localization of cathepsinBduring the progression of human gliomas. Clin Exp Metastasis 13(1): 49–56, 1995Google Scholar
  5. 5.
    Sivaparvathi M, Yamamoto M, Nicolson GL, Gokaslan ZL, Fuller GN, Liotta LA, Sawaya R, Rao JS: Expression and immunohistochemical localization of cathepsin L during the progression of human gliomas. Clin Exp Metastasis 14(1): 27–34, 1996Google Scholar
  6. 6.
    Yamamoto M, Sawaya R, Mohanam S, Rao VH, Bruner JM, Nicolson GL, Rao JS: Expression and localisation of urokinase-type plasminogen activator receptor in human gliomas. Cancer Res 54(18): 5016–5020, 1994Google Scholar
  7. 7.
    Sawaya RE, Yamamoto M, Gokaslan ZL, Wang SW, Mohanam S, Fuller GN, McCutcheon IE, Stetler-Stevenson WG, Nicolson GL, Rao JS: Expression and localization of 72 kDa type IV collagenase (MMP-2) in human malignant gliomas in vivo. Clin Exp Metastasis 14: 35–42, 1996Google Scholar
  8. 8.
    Rooprai HK, McCormick D: Proteases and their inhibitors in brain tumours: a review. Anticancer Res 17: 4152–4162, 1997Google Scholar
  9. 9.
    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, 1999Google Scholar
  10. 10.
    Apodaca G, Rutka JT, Bouhana K, Berens ME, Giblin JR, Rosenblum ML, McKerrow JH, Banda MJ: Expression of matrix metalloproteinases and metalloproteinase inhibitors by fetal astrocytes and glioma cells. Cancer Res 50(8): 2322–2329, 1990Google Scholar
  11. 11.
    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, 1995Google Scholar
  12. 12.
    Kachra Z, Beaulieu E, Delbecchi L, Mousseau N, Berthelet F, Moumdjian R, Del Maestro R, Beliveau R: Expression of matrix metalloproteinases and their inhibitors in human brain tumors. Clin Exp Metastasis 177(7): 555s–566, 1999Google Scholar
  13. 13.
    Freidberg MH, Glantz MJ, Klempner MS, Cole BF, Perides G: Specific matrix metalloproteinase profiles in the cerebral spinal fluid correlated with the presence of malignant astrocytomas, brain metastases, and carcinomatous meningitis. Cancer 82: 923–930, 1998Google Scholar
  14. 14.
    Forsyth PA, Laing TD, Gibson AW, Rewcastle NB, Brasher P, Sutherland G, Johnston RN, Edwards DR: High levels of gelatinase B and active gelatinase A in metastatic glioblastoma. J Neuro-Oncol 36: 21–29, 1998Google Scholar
  15. 15.
    Deryugina EI, Luo GX, Reisfeld RA, Bourdon MA, Strongin A: Tumor cell invasion through matrigel is regulated by activated matrix metalloproteinase-2. Anticancer Res 17(5A): 3201–3210, 1997Google Scholar
  16. 16.
    Deryugina EI, Bourdon MA, Luo GX, Reisfeld RA, Strongin A: Matrix metalloproteinase-2 activation modulates glioma cell migration. J Cell Sci 110(Pt 19): 2473–2482, 1997Google Scholar
  17. 17.
    Senota A, Itoh F, Yamamoto H, Adachi Y, Hinoda Y, Imai K: Relation of matrilysin messenger RNA expression with invasive activity in human gastric cancer. Clin Exp Metastasis 16(4): 313–321, 1998Google Scholar
  18. 18.
    Goldberg GI, Wilhelm SM, Kronberger A, Bauer EA, Grant GA, Eisen AZ: Human fibroblast collagenase: complete primary structure and homology to an oncogene transformation-induced rat protein. J Biol Chem 261: 6600–6605, 1986Google Scholar
  19. 19.
    Brinckerhoff CE, Ruby PL, Austin SD, Fini ME, White HD: Molecular cloning of human synovial cell collagenase and selection of a single gene from genomicDNA. J Clin Invest 79: 542–546, 1987Google Scholar
  20. 20.
    Huhtala P, Eddy RL, Fan YS, Byers MG, Shows TB, Tryggvason K: Completion of the primary structure of the human type IV collagenase preproenzyme and assignment of the gene (CLG4) to the q21 region of chromosome 16. Genomics 6: 554–559, 1990Google Scholar
  21. 21.
    Collier IE, Bruns GAP, Goldberg GI, Gerhard DS: On the structure and chromosome location of the 72-and 92-kDa human type IV collagenase genes. Genomics 9: 429–434, 1991Google Scholar
  22. 22.
    Whitham SE, Murphy G, Angel P, Rahmsdorf HJ, Smith BJ, Lyons A, Harris TJ, Reynolds JJ, Herrlich P, Docherty AJ: Comparison of human stromelysin and collagenase by cloning and sequence analysis. Biochem J 240: 913–916, 1986Google Scholar
  23. 23.
    Spurr NK, Gough AC, Gosden J, Rout D, Porteous DJ, van Heyningen V, Docherty AJP: Restriction fragment length polymorphism analysis and assignment of the metalloproteinases stromelysin and collagenase to the long arm of chromosome 11. Genomics 2: 119–127, 1988Google Scholar
  24. 24.
    Muller D, Quantin B, Gesnel M-C, Millon-Collard R, Abecassis J, Breathnach R: The collagenase gene family in humans consists of at least four members. Biochem J 253: 187–192, 1988Google Scholar
  25. 25.
    Gaire M, Magbanua Z, McDonnell S, McNeil L, Lovett DH, Matrisian L: Structure and expression of the human gene for the matrix metalloproteinase matrilysin. J Biol Chem 269: 2032–2040, 1994Google Scholar
  26. 26.
    Hasty KA, Pourmotabbed TF, Goldberg GI, Thompson JP, Spinella DG, Stevens RM, Mainardi CL: Human neutrophil collagenase: a distinct gene product with homology to other matrix metalloproteinases. J Biol Chem 265: 11421–11424, 1990Google Scholar
  27. 27.
    Yang-Feng TL, Berliner N, Deverajan P, Johnston J: Assignment of two human neutrophil secondary granule protein genes, transcobalamin I and neutrophil collagenase to chromosome 11 (Abstract) Cytogenet Cell Genet 58: 1974, 1991Google Scholar
  28. 28.
    Huhtala P, Tuuttila A, Chow LT, Lohi J, Keski-Oja J, Tryggvason K: Complete structure of the human gene for 92-kDa type IV collagenase: divergent regulation of expression for the 92-and 72-kilodalton enzyme genes in HT-1080 cells. J Biol Chem 266: 16485–16490, 1991Google Scholar
  29. 29.
    Jung JY, Warter S, Rumpler Y: Localization of stromelysin 2 gene to the q22.3–23 region of chromosome 11 by in situ hybridization. Ann Genet 33: 21–23, 1990Google Scholar
  30. 30.
    Formstone CJ, Byrd PJ, Ambrose HJ, Riley JH, Hernandez D, McConville CM, Taylor AMR: The order and orientation of a cluster of metalloproteinase genes, stromelysin 2, collagenase, and stromelysin, together with D11S385, on chromosome 11q22-q23. Genomics 16: 289–291, 1993Google Scholar
  31. 31.
    Levy A, Zuchman J, Delattre O, Mattei M-G, Rio M-C, Basset P: Assignment of the human stromelysin 3 (STMY3) gene to the q11.2 region of chromosome 22. Genomics 13: 881–883, 1992Google Scholar
  32. 32.
    Shapiro SD, Kobayashi DK, Ley TJ: Cloning and characterization of a unique elastolytic metalloproteinase produced by human alveolar macrophages. J Biol Chem 268: 23824–23829, 1993Google Scholar
  33. 33.
    Belaaouaj A, Shipley JM, Kobayashi DK, Zimonjic DB, Popescu N, Silverman GA, Shapiro SD: Human macrophage metalloelastase: genomic organization, chromosomal location, gene linkage, and tissue-specific expression. J Biol Chem 270: 14568–14575, 1995Google Scholar
  34. 34.
    Pendas AM, Matilla T, Estivill X, Lopez-Otin C: The human collagenase-3 (CLG3) gene is located on chromosome 11q22.3 clustered to other members of the matrix metalloproteinase gene family. Genomics 26: 615–618, 1995Google Scholar
  35. 35.
    Mitchell PG, Magna HA, Reeves LM, Lopresti-Morrow LL, Yocum SA, Rosner PJ, Geoghegan KF, Hambor JE: Cloning, expression, and type II collagenolytic activity of matrix metalloproteinase-13 from human osteoarthritic cartilage. J Clin Invest 97: 761–768, 1996Google Scholar
  36. 36.
    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, 1994Google Scholar
  37. 37.
    Mattei M-G, 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: 168–169, 1997Google Scholar
  38. 38.
    Will H, Hinzmann B: cDNA sequence and mRNA tissue distribution of a novel human matrix metalloproteinase with a potential transmembrane segment. Eur J Biochem 231: 602–608, 1995Google Scholar
  39. 39.
    Takino T, Sato H, Shinagawa A, Seiki M: Identification of the second membrane-type matrix metalloproteinase (MT-MMP-2) gene from a human placenta cDNA library: MT-MMPs form a unique membrane-type subclass in the MMP family. J Biol Chem 270: 23013–23020, 1995Google Scholar
  40. 40.
    Sato H, Tanaka M, Takino T, Inoue M, Seiki M: Assignment of the human genes for membrane-type-1,-2, and-3 matrix metalloproteinases (MMP14, MMP15, and MMP16) to 14q12.2, 16q12.2-q21, and 8q21, respectively, by in situ hybridization. Genomics 39: 412–413, 1997Google Scholar
  41. 41.
    Puente XS, Pendas AM, Llano E, Velasco G, Lopez-Otin C: Molecular cloning of a novel membranetype matrix metalloproteinase from a human breast carcinoma. Cancer Res 56(5): 944–949, 1996Google Scholar
  42. 42.
    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: 578–579, 1998Google Scholar
  43. 43.
    Stolow MA, Bauzon DD, Li J, Sedgwick T, Liang VC, Sang QA, Shi YB: Identification and characterization of a novel collagenase in Xenopus laevis: possible roles during frog development. Mol Biol Cell 7(10): 1471–1483, 1996Google Scholar
  44. 44.
    Pendas AM, Knauper V, Puente XS, Llano E, Mattei MG, Apte S, Murphy G, Lopez-Otin C: Identification and characterization of a novel human matrix metalloproteinase with unique structural characteristics, chromosomal location, and tissue distribution. J Biol Chem 272(7): 4281–4286, 1997Google Scholar
  45. 45.
    Sedlacek R, Mauch S, Kolb B, Schatzlein C, Eibel H, Peter HH, Schmitt J, Krawinkel U: Matrix metalloproteinase MMP-19 (RASI-1) is expressed on the surface of activated peripheral blood mononuclear cells and is detected as an autoantigen in rheumatoid arthritis. Immunobiology 198(4): 408–423, 1998Google Scholar
  46. 46.
    Llano E, Pendas AM, Knauper V, Sorsa T, Salo T, Salido E, Murphy G, Simmer JP, Bartlett JD, Lopez-Otin sC: Identification and structural and functional characterization of human enamelysin (MMP-20). Biochemistry 36: 15101–15108, 1997Google Scholar
  47. 47.
    Yang M, Murray MT, Kurkinen M: Anovel matrix metalloproteinase gene (XMMP) encoding vitronectin-like motifs is transiently expressed in Xenopus laevis early embryo development. J Biol Chem 272(21): 13527–13533, 1997Google Scholar
  48. 48.
    Yang M, Kurkinen M: Cloning and characterization of a novel matrix metallo-proteinase (MMP), CMMP, from chicken embryo fibroblasts. CMMP, Xenopus XMMP, and human MMP19 have a conserved unique cysteine in the catalytic domain. J Biol Chem 273(28): 17893–17900, 1998Google Scholar
  49. 49.
    Gururajan R, Grenet J, Lahti JM, Kidd VJ: Isolation and characterization of two novel metalloproteinase genes linked to the Cdc2L locus on human chromosome 1p36.3. Genomics 52: 101–106, 1998Google Scholar
  50. 50.
    Velasco G, Pendas AM, Fueyo A, Knauper V, Murphy G, Lopez-Otin C: Cloning and characterization of human MMP-23, a new matrix metalloproteinase predominantly expressed in reproductive tissues and lacking conserved domains in other family members. J Biol Chem 274(8): 4570–4576, 2000Google Scholar
  51. 51.
    Llano E, Pendas AM, Freije JP, Nakano A, Knauper V, Murphy G, Lopez-Otin C: Identification and characterization of human MT5-MMP, a new membrane-bound activator of progelatinase A over-expressed in brain tumors. Cancer Res 59: 2570–2576, 1999Google Scholar
  52. 52.
    Pei D: Leukolysin/MMP25/MT6-MMP: a novel matrix metalloproteinase specifically expressed in the leukocyte lineage. Cell Res 9(4): 291–303, 1999Google Scholar
  53. 53.
    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, 2000Google Scholar
  54. 54.
    de Coignac AB, Elson G, Delneste Y, Magistrelli G, Jeannin P, Aubry JP, Berthier O, Schmitt D, Bonnefoy JY, Gauchat JF: Cloning of MMP-26. A novel matrilysin-like proteinase. Eur J Biochem 267(11): 3323–3329, 2000Google Scholar
  55. 55.
    Lohi J, Wilson CA, Roby JD, Parks WC: Epilysin, a novel human matrix metalloproteinase (MMP-28) expressed in testis and keratinocytes in response to injury. J Biol Chem 276(13): 10134–10144, 2001Google Scholar
  56. 56.
    Yong VW, Krekoski CA, Forsyth PA, Bell R, Edwards DR: Matrix metallo-proteinases and diseases of the CNS. Trends Neurosci 21(2): 75–80, 1999Google Scholar
  57. 57.
    Graesser D, Mahooti S, Madri JA: McLendon RE: Ham56-immunoreactive macrophages in untreated infiltrating gliomas. Arch Pathol Lab Med 125(5): 637–41, 2001Google Scholar
  58. 58.
    Vos CM, Gartner S, Ransohoff RM, McArthur JC, Wahl L, Sjulson L, Hunter E, Conant K: Matrix metalloprotease-9 release from monocytes increases as a function of differentiation: implications for neuroinflammation and neurodegeneration. J Neuroimmunol 109(2): 221–227, 2000Google Scholar
  59. 59.
    Abe T, Mori T, Kohno K, Seiki M, Hayakawa T, Welgus HG, Hori S, Kuwano M: Expression of 72 kDa type IV collagenase and invasion activity of human glioma cells. Clin Exp Metastasis 12(4): 296–304, 1994Google Scholar
  60. 60.
    Van Meter T, Rooprai HK, Rucklidge GJ, Pilkington GJ: Functional blocking with TIMP-1 and anti-alpha-V integrin: evidence for cooperation of MMPs and integrins in glioma invasion in vitro. Anticancer Res 17: 1051, 1997 (Abstract)Google Scholar
  61. 61.
    Matsuzawa K, Fukuyama K, Hubbard SL, Dirks PB, Rutka JT: Transfection of an invasive human astrocytoma cell line with a TIMP-1 cDNA: modulation of astrocytoma invasive potential. J Neuropathol Exp Neurol 55(1): 88–96, 1996Google Scholar
  62. 62.
    Merzak A, Parker C, Koochekpour S, Sherbet GV, Pilkington GJ: Overexpression of the 18A2/mts1 gene and down-regulation of the TIMP-2 gene in invasive human glioma cell lines in vitro. Neuropathol Appl Neurobiol 20(6): 614–619, 1994Google Scholar
  63. 63.
    Pagenstecher A, Stalder AK, Campbell IL: RNAse protection assays for the simultaneous and semiquantitative analysis of multiple murine matrix metalloproteinase (MMP) and MMP inhibitor mRNAs. J Immunol Methods 206(1–2): 1–9, 1997Google Scholar
  64. 64.
    Weeks BS: The role of HIV-1 activated leukocyte adhesion: mechanisms and matrix metalloproteinase secretion in AIDS pathogenesis. Int J Mol Med 1(2): 361–366, 1996Google Scholar
  65. 65.
    Gasche Y, Fujimura M, Morita-Fujimura Y, Copin JC, Kawase M, Massengale J, Chan PH: Early appearance of activated matrix metalloproteinase-9 after focal cerebral ischemia in mice: a possible role in blood-brain barrier dysfunction. J Cereb Blood Flow Metab 19(9): 1020–1028, 1999Google Scholar
  66. 66.
    Rosenberg GA, Dencoff JE, McGuire PG, Liotta LA, Stetler-Stevenson WG: Injury-induced 92-kilodalton gelatinase and urokinase expression in rat brain. Lab Invest 71(3): 417–422, 1994Google Scholar
  67. 67.
    Wang X, Jung J, Asahi M, Chwang W, Russo L, Moskowitz MA, Dixon CE, Fini ME, Lo EH: Effects of matrix metalloproteinase-9 gene knock-out on morphological and motor outcomes after traumatic brain injury. J Neurosci 20(18): 7037–7042, 2000Google Scholar
  68. 68.
    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): 1153–1157, 1998Google Scholar
  69. 69.
    Maeda A, Sobel RA: Matrix metalloproteinases in the normal human central nervous system, microglial nodules, and sclerosis lesions. J Neuropathol Exp Neurol 55(3): 300–309, 1996Google Scholar
  70. 70.
    Madri JA, Graesser D, Haas T: The roles of adhesion molecules and proteinases in lymphocyte transendothelial migration. Biochem Cell Biol 74(6): 749–757, 1996Google Scholar
  71. 71.
    Graesser D, Mahooti S, Madri JA: Distinct roles for matrix metalloproteinase-2 and alpha4 integrin in autoimmune T cell extravasation and residency in brain parenchyma during experimental autoimmune encephalomyelitis. J Neuroimmunol 109(2): 121–131, 2000Google Scholar
  72. 72.
    Esteve PO, Tremblay P, Houde M, St-Pierre Y, Mandeville R: In vitro expression of MMP-2 and MMP-9 in glioma cells following exposure to inflammatory mediators. Biochim Biophys Acta 1403(1): 85–96, 1998Google Scholar
  73. 73.
    Rooprai HK, Rucklidge GJ, Panou C, Pilkington GJ: The effects of exogenous growth factors on matrix metalloproteinase secretion by human brain tumour cells. Br J Cancer 82(1): 52–53, 2000Google Scholar
  74. 74.
    Gottschall PE, Yu X: Cytokines regulate gelatinase A and B (matrix metalloproteinase 2 and 9) activity in cultured ratastrocytes. J Neurochem 64(4): 1513–1520, 1995Google Scholar
  75. 75.
    Liuzzi GM, Santacroce MP, Peumans WJ, Van Damme EJ, Dubois B, Opdenakker G, Riccio P: Regulation of gelatinases in microglia and astrocyte cell cultures by plant lectins. Glia 27(1): 53–61, 1999Google Scholar
  76. 76.
    Qin H, Sun Y, Benveniste EN: The transcription factors Sp1, Sp3, and AP-2 are required for constitutive matrix metalloproteinase-2 gene expression in astroglioma cells. J Biol Chem 274(41): 29130–29137, 1999Google Scholar
  77. 77.
    Ozaki I, Mizuta T, Zhao G, Yotsumoto H, Hara T, Kajihara S, Hisatomi A, Sakai T, Yamamoto K: Involvement of the Ets-1 gene in over-expression of matrilysin in human hepatocellular carcinoma. Cancer Res 60(22): 6519–6525, 2000Google Scholar
  78. 78.
    Westermarck J, Seth A, Kahari VM: Differential regulation of interstitial collagenase (MMP-1) gene expression by ETS transcription. Oncogene 14(22): 2651–2660, 1997Google Scholar
  79. 79.
    Watabe T, Yoshida K, Shindoh M, Kaya M, Fujikawa K, Sato H, Seiki M, Ishii S, Fujinaga K: The Ets-1 and Ets-2 transcription factors activate the promoters for invasionassociated urokinase and collagenase genes in response to epidermal growth factor. Int J Cancer 77(1): 128–137, 1998Google Scholar
  80. 80.
    Himelstein BP, Lee EJ, Sato H, Seiki M, Muschel RJ: Tumor cell contact mediated transcriptional activation of the fibroblast matrix metalloproteinase-9: involvement of multiple transcription factors including Ets and an alternating purine-pyrimidine repeat. Clin Exp Metastasis 16(2): 169–177, 1998Google Scholar
  81. 81.
    Sato H, Seiki M: Regulatory mechanism of 92 kDa type IV collagenase gene expression which is associated with invasiveness of tumor cells. Oncogene 8(2): 395–405, 1993Google Scholar
  82. 82.
    Kerr LD, Holt JT, Matrisian LM: Growth factors regulate transin gene expression by c-fos-dependent and c-fosindependent pathways. Science 242: 1424–1427, 1988Google Scholar
  83. 83.
    Eberhardt W, Huwiler A, Beck KF, Walpen S, Pfeilschifter J: Amplification of IL-1 beta-induced matrix metalloproteinase-9 expression by superoxide in rat glomerular mesangial cells is mediated by increased activities of NF-kappa B and activating protein-1 and involves activation of the mitogen-activated protein kinase pathways. J Immunol 165(10): 5788–5797, 2000Google Scholar
  84. 84.
    Chintala SK, Sawaya R, Aggarwal BB, Majumder S, Giri DK, Kyritsis AP, Gokaslan ZL, Rao JS: Induction of matrix metalloproteinase-9 requires a polymerized actin cytoskeleton in human malignant glioma cells. J Biol Chem 273(22): 13545–13551, 1998Google Scholar
  85. 85.
    Meade-Tollin LC, Boukamp P, Fusenig NE, Bowen CP, Tsang TC, Bowden GT: Differential expression of matrix metalloproteinases in activated c-ras-Ha-transfected immortalized human keratinocytes. Br J Cancer 77(5): 724–730, 1998Google Scholar
  86. 86.
    Himelstein BP, Lee EJ, Sato H, Seiki M, Muschel RJ: Transcriptional activation of the matrix metalloproteinase-9 gene in an H-ras and v-myc transformed rat embryo cell line. Oncogene 14(16): 1995–1998, 1997Google Scholar
  87. 87.
    Imai K, Yokohama Y, Nakanishi I, Ohuchi E, Fujii Y, Nakai N, Okada Y:Matrix metalloproteinase 7 (matrilysin) from human rectal carcinoma cells. Activation of the precursor, interaction with other matrix metalloproteinases and enzymic properties. J Biol Chem 270(12): 6691–6697, 1995Google Scholar
  88. 88.
    Crabbe T, O'Connell JP, Smith BJ, Docherty AJ: Reciprocated matrix metalloproteinase activation: a process performed by interstitial collagenase and progelatinase A. Biochemistry 33(48): 14419–14425, 1994Google Scholar
  89. 89.
    Docherty AJP, Lyons A, Smith BJ, Wright EM, Stephens PE, Harris TJR: Sequence of human tissue inhibitor of metalloproteinases and its identity to erythroidpotentiating activity. Nature 318: 66–69, 1985Google Scholar
  90. 90.
    Hammani K, Blakis A, Morsette D, Bowcock AM, Schmutte C, Henriet P, DeClerck YA: Structure and characterization of the human tissue inhibitor of metalloproteinases-2 gene. J Biol Chem 271: 25498–25505, 1996Google Scholar
  91. 91.
    Wilde CG, Hawkins PR, Coleman RT, Levine WB, Delegeane AM, Okamoto PM, Ito LY, Scott RW, Seilhamer JJ: Cloning and characterization of human tissue inhibitor of metalloproteinases-3. DNA. Cell Biol 13: 711–718, 1994Google Scholar
  92. 92.
    Greene J, Wang M, Liu YE, Raymond LA, Rosen C, Shi YE: Molecular cloning and characterization of human tissue inhibitor of metalloproteinase 4. J Biol Chem 271: 30375–30380, 1996Google Scholar
  93. 93.
    Gomez DE, Alonso DF, Yoshiji H, Thorgeirsson UP: Tissue inhibitors of metalloproteinases: structure, regulation and biological functions. Eur J Cell Biol 74(2): 111–122, 1997Google Scholar
  94. 94.
    Planchenault T, Costa S, Fages C, Riche D, Charriere-Bertrand C, Perzelova A, Meimon G, Tardy M: Differential expression of laminin and fibronectin and of their related metalloproteinases in human glioma cell lines: relation to invasion. Lett 299(1–2): 140–144, 2001Google Scholar
  95. 95.
    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(2): 429–437, 1998Google Scholar
  96. 96.
    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 and dissemination of human malignant glioma. J Neurosurg 94(3): 464–473, 2001Google Scholar
  97. 97.
    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, 1996Google Scholar
  98. 98.
    Emmert-Buck MR, Emonard HP, Corcoran ML, Krutzsch HC, Foidart JM, Stetler-Stevenson WG: Cell surface binding of TIMP-2 and pro-MMP-2/TIMP-2 complex. FEBS Lett 364(1): 28–32, 1995Google Scholar
  99. 99.
    Shofuda K, Moriyama K, Nishihashi 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 progelatinase A activation catalyzed by membrane-type matrix metalloproteinase-1 (MT1-MMP) in human cancer cells. Biochem (Tokyo) 124(2): 462–470, 1998Google Scholar
  100. 100.
    Knauper V, Will H, Lopez-Otin C, Smith B, Atkinson SJ, Stanton H, Hembry RM, Murphy G: Cellular mechanisms for human procollagenase-3 (MMP-13) activation. Evidence that MT1-MMP (MMP-14) and gelatinase a (MMP-2) are able to generate active enzyme. J Biol Chem 271(29): 17124–17131, 1996Google Scholar
  101. 101.
    Fridman R, Toth M, Pena D, Mobashery S: Activation of progelatinase B (MMP-9) by gelatinase A (MMP-2). Cancer Res 55(12): 2548–2555, 1995Google Scholar
  102. 102.
    Harayama T, Ohuchi E, Aoki T, Sato H, Seiki M, Okada Y: Shedding of membrane type 1 matrix metalloproteinase in a human breast carcinoma cell line. Jpn J Cancer Res 90(9): 942–950, 1999Google Scholar
  103. 103.
    Pei D: Identification and characterization of the fifth membrane-type matrix metalloproteinase MT5-MMP. J Biol Chem 274(13): 8925–8932, 1999Google Scholar
  104. 104.
    Knauper V, Murphy G: Membrane-type metalloproteinases and cell surface-associated activation cascades for matrix metalloproteinases. In: Matrix Metallo-proteinases, Parks WC, Mecham MP (eds), Academic Press, London, 1998, pp 199–218Google Scholar
  105. 105.
    Sun Y, Sun Y, Wenger L, Rutter JL, Brinckerhoff CE, Cheung HS: P53 downregulates regulates human matrix metalloproteinase-1 (Collagenase-1) gene expression. J Biol Chem 274(17): 11535–11540, 1999Google Scholar
  106. 106.
    Bian J, Sun Y: Transcriptional activation by p53 of the human type IV collagenase (gelatinase A or matrix metalloproteinase 2) promoter. Mol Cell Biol 17(11): 6330–6338, 1997Google Scholar
  107. 107.
    Sun Y, Cheung JM, Martel-Pelletier J, Pelletier JP, Wenger L, Altman RD, Howell DS, Cheung HS: Wild type and mutant p53 differentially regulate the gene expression of human collagenase-3 (hMMP-13). J Biol Chem 275(15): 11327–11332, 2000Google Scholar
  108. 108.
    Ossowski L, Aguirre-Ghiso JA: Urokinase receptor and integrin partnership: coordination of signaling for cell adhesion, migration and growth. Curr Opin Cell Biol 12(5): 613–620, 2000Google Scholar
  109. 109.
    Saito S, Yamaji N, Yasunaga K, Saito T, Matsumoto S, Katoh M, Kobayashi S, Masuho Y: The fibronectin extra domain A activates matrix metalloproteinase gene expression by an interleukin-1-dependent mechanism. J Biol Chem 274(43): 30756–30763, 1999Google Scholar
  110. 110.
    Pender SL, Salmela MT, Monteleone G, Schnapp D, McKenzie C, Spencer J, Fong S, Saarialho-Kere U, MacDonald TT: Ligation of alpha4beta1 integrin on human intestinal mucosal mesenchymal cells selectively up-regulates membrane type-1 matrix metallo-proteinase and confers a migratory phenotype. Am J Pathol 157(6): 1955–1962, 2000Google Scholar
  111. 111.
    Millward-Sadler SJ, Wright MO, Davies LW, Nuki G, Salter DM: Mechano-transduction via integrins and interleukin-4 results in altered aggrecan and matrix metalloproteinase 3 gene expression in normal, but not osteoarthritic, human articular chondrocytes. Arthritis Rheum 43(9): 2091–2099, 2000Google Scholar
  112. 112.
    Giambernardi TA, Grant GM, Taylor GP, Hay RJ, Maher VM, McCormick JJ, Klebe RJ: Overview of matrix metalloproteinase expression in cultured human cells. Matrix Biol 16(8): 483–496, 1998Google Scholar
  113. 113.
    Rooprai HK, VanMeter T, Panou C, Schnull S, Trillo-Pazos G, Davies D, Pilkington GJ: The role of integrin receptors in aspects of glioma invasion in vitro. Int J Dev Neurosci 17(5–6): 613–623, 1999Google Scholar
  114. 114.
    Matsuzawa K, Fukuyama K, Hubbard SL, Dirks PB, Rutka JT: Transfection of an invasive human astrocytoma cell line with a TIMP-1 cDNA: modulation of astrocytoma invasive potential. J Neuropathol Exp Neurol 55(1): 88–96, 1996Google Scholar
  115. 115.
    Tonn JC, Kerkau S, Hanke A, Bouterfa H, Mueller JG, Wagner S, Vince GH, Roosen K: Effect of synthetic matrix-metalloproteinase inhibitors on invasive capacity and proliferation of human malignant gliomas in vitro. Int J Cancer 80(5): 764–772, 1999Google Scholar
  116. 116.
    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(3): 464–473, 2001Google Scholar
  117. 117.
    Treasurywala S, Berens ME: Migration arrest in glioma cells is dependent on the alphav integrin subunit. Glia 24(2): 236–243, 1998Google Scholar
  118. 118.
    Gilles C, Bassuk JA, Pulyaeva H, Sage EH, Foidart JM, Thompson EW: SPARC/osteonectin induces matrix metalloproteinase 2 activation in human breast cancer cell lines. Cancer Res 58(23): 5529–5536, 1998Google Scholar
  119. 119.
    Crawford HC, Fingleton B, Gustavson MD, Kurpios N, Wagenaar RA, Hassell JA, Matrisian LM: The PEA3 subfamily of Ets transcription factors synergizes with beta-catenin-LEF-1 to activate matrilysin transcription in intestinal tumors. Mol Cell Biol 21(4): 1370–1383, 2001Google Scholar
  120. 120.
    Tajima A, Miyamoto Y, Kadowaki H, Hayashi M: Mouse integrin alphav promoter is regulated by transcriptional factors Ets and Sp1 in melanoma cells. Biochim Biophys Acta 1492(2–3): 377–384, 2000Google Scholar
  121. 121.
    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, 1999Google Scholar
  122. 122.
    Nagashima Y, Hasegawa S, Koshikawa N, Taki A, Ichikawa Y, Kitamura H, Misugi K, Kihira Y, Matuo Y, Yasumitsu H, Miyazaki K: Expression of matrilysin in vascular endothelial cells adjacent to matrilysin-producing tumors. Int J Cancer 72(3): 441–445, 1997Google Scholar
  123. 123.
    Raithatha SA, Muzik H, Muzik H, Rewcastle NB, Johnston RN, Edwards DR, Forsyth PA: Localization of gelatinase-A and gelatinase-B mRNA and protein in human gliomas. Neuro-Oncol 2(3): 145–150, 2000Google Scholar
  124. 124.
    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, 1983Google Scholar
  125. 125.
    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 matrix metalloproteinases in human astrocytic tumors. Am J Pathol 154(2): 417–428, 1999Google Scholar
  126. 126.
    Shofuda K, Yasumitsu H, Nishihashi A, Miki K, Miyazaki K: Expression of three membrane-type matrix metalloproteinases (MT-MMPs) in rat vascular smooth muscle cells and characterization of MT3-MMPs with and without transmembrane domain. J Biol Chem 272(15): 9749–9754, 1997Google Scholar
  127. 127.
    Pagenstecher A, Stalder AK, Campbell IL: RNAse protection assays for the simultaneous and semiquantitative analysis of multiple murine matrix metalloproteinase (MMP) and MMP inhibitor mRNAs. J Immunol Methods 206(1–2): 1–9, 1997Google Scholar
  128. 128.
    Ishikawa T, Ichikawa Y, Mitsuhashi M, Momiyama N, Chishima T, Tanaka K, Yamaoka H, Miyazakic K, Nagashima Y, Akitaya T, Shimada H: Matrilysin is associated with progression of colorectal tumor. Cancer Lett 107(1): 5–10, 1996Google Scholar
  129. 129.
    Adachi Y, Itoh F, Yamamoto H, Matsuno K, Arimura Y, Kusano M, Endoh T, Hinoda Y, Oohara M, Hosokawa M, Imai K: Matrix metalloproteinase matrilysin (MMP-7) participates in the progression of human gastric and esophageal cancers. Int J Oncol 13(5): 1031–1035, 1998Google Scholar
  130. 130.
    Ohashi K, Nemoto T, Nakamura K, Nemori R: Increased expression of matrix metalloproteinase 7 and 9 and membrane type 1-matrix metalloproteinase in esophageal squamous cell carcinomas. Cancer 88(10): 2201–2209, 2000Google Scholar
  131. 131.
    Nguyen M, Arkell J, Jackson CJ: Active and tissue inhibitor of matrix metalloproteinase-free gelatinase B accumulates within human microvascular endothelial vesicles. J Biol Chem 273(9): 5400–5404, 1998Google Scholar
  132. 132.
    von Bredow DC, Cress AE, Howard EW, Bowden GT, Nagle RB: Activation of gelatinase-tissue-inhibitors-ofmetalloproteinase complexes by matrilysin. Biochem J 331(Pt 3): 965–972, 1998Google Scholar
  133. 133.
    Nakahara H, Howard L, Thompson EW, Sato H, Seiki M, Yeh Y, Chen WT: Transmembrane/cytoplasmic domainmediated membrane type 1-matrix metalloprotease docking toinvadopodia is required for cell invasion. Proc Natl Acad Sci USA 94(15): 7959–7964, 1997Google Scholar
  134. 134.
    Tonn JC, Wunderlich S, Kerkau S, Klein CE, Roosen K: Invasive behaviour of human gliomas is mediated by interindividually different integrin patterns. Anticancer Res 18(4A): 2599–2605, 1998Google Scholar
  135. 135.
    Paulus W, Baur I, Schuppan D, Roggendorf W: Characterization of integrin receptors in normal and neoplastic human brain. Am J Pathol 143(1): 154–163, 1993Google Scholar
  136. 136.
    Chintala SK, Sawaya R, Gokaslan ZL, Rao JS: Modulation of matrix metalloprotease-2 and invasion in human glioma cells by alpha 3 beta 1 integrin. Cancer Lett 103(2): 201–208, 1996Google Scholar
  137. 137.
    Ellerbrock SM, Fishman DA, Kerns AS, Bafetti LM, Stack MS: Ovarian carcinoma regulation of matrix metalloproteinase-2 and membrane type 1 matrix metalloproteinase through beta 1 integrin. Cancer Res 59: 1635–1641, 1999Google Scholar
  138. 138.
    Berditchevski F, Chang S, Bodorova J, Hemler ME: Generation of monoclonal antibodies to integrinassociated proteins. Evidence that alpha3 beta1 complexes with EMMPRIN/basigin/OX47/M6. J Biol Chem 272(46): 29174–29180, 1997Google Scholar
  139. 139.
    Sameshima T, Nabeshima K, Toole BP, Yokogami K, Okada Y, Goya T, Koono M, Wakisaka S: Expression of emmprin (CD147), a cell surface inducer of matrix metalloproteinases, in normal human brain and gliomas. Int J Cancer 88(1): 21–27, 2000Google Scholar
  140. 140.
    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, 2000Google Scholar
  141. 141.
    Milner R, French-Constant C: A developmental analysis of oligodendroglial integrins in primary cells: changes in alphav-associated beta subunits during differentiation. Development 120(12): 3497–3506, 1994Google Scholar
  142. 142.
    Decker L, Avellana-Adalid V, Nait-Oumesmar B, Durbec P, Baron-Van Evercooren A: Oligodendrocyte precursor migration and differentiation: combined effects of PSA residues, growth factors, and substrates. Mol Cell Neurosci 16(4): 422–439, 2000Google Scholar
  143. 143.
    Paulus W, Baur I, Huettner C, Schmausser B, Roggendorf W, Schlingensiepen KH, Brysch W: Effects of transforming growth factor-beta 1 on collagen synthesis, integrin expression, adhesion and invasion of glioma cells. J Neuropathol Exp Neurol 54(2): 236–244, 1995Google Scholar
  144. 144.
    Miyake K, Kimura S, Nakanishi M, Hisada A, Hasegawa M, Nagao S, Abe Y: Transforming growth factor-beta1 stimulates contraction of human glioblastoma cell-mediated collagen lattice through enhanced alpha2 integrin expression. J Neuropathol Exp Neurol 59(1): 18–28, 2000Google Scholar
  145. 145.
    Platten M, Wick W, Wild-Bode C, Aulwurm S, Dichgans J, Weller M: Transforming growth factors beta(1) (TGFbeta( 1)) and TGF-beta(2) promote glioma cell migration via up-regulation of alpha(V)beta(3) integrin expression. Biochem Biophys Res Commun 268(2): 607–611, 2000Google Scholar
  146. 146.
    Tajima A, Miyamoto Y, Kadowaki H, Hayashi M: Mouse integrin alphav promoter is regulated by transcriptional factors Ets and Sp1 in melanoma cells. Biochim Biophys Acta 1492(2–3): 377–384, 2000Google Scholar
  147. 147.
    Ozaki I, Mizuta T, Zhao G, Yotsumoto H, Hara T, Kajihara S, Hisatomi A, Sakai T, Yamamoto K: Involvement of the Ets-1 gene in overexpression of matrilysin in human hepatocellular carcinoma. Cancer Res 60(22): 6519–6525, 2000Google Scholar
  148. 148.
    Rooprai HK, Kandanearatachi A, Rucklidge G, Pilkington GJ: Influence of putative antiinvasive agents on matrix metalloproteinase secretion by human neoplastic glia in vitro. Ann NY Acad Sci 878: 654–657, 1999Google Scholar
  149. 149.
    Rooprai HK, Kanandearatchi A, Maidment SL, Christidou M, Trillo-Pazos G, Dexter DT, Rucklidge GJ, Widmer W, Pilkington GJ: Evaluation of the effects of swainsonine, captopril, tangeretin and nobiletin on the biological behaviour of brain tumour cells in vitro. Neuropath Appl Neurobiol 27: 29–39, 2001Google Scholar
  150. 150.
    Seftor REB, Seftor EA, Grimes WJ, Liotta LA, Stetler-Stevenson WG, Welch DR, Hendrix MJ:Humanmelanoma cell invasion is inhibited in vitro by swainsonine and deoxymannojirimycin with a concomitant decrease in collagenase IV expression. Melanoma Res 1: 43–54, 1981Google Scholar
  151. 151.
    Planus E, Barlovatz-Meimon G, Rogers RA, Bonavaud S, Ingber DE, Wang N: Binding of urokinase to plasminogen activator inhibitor type-1 mediates cell adhesion and spreading. J Cell Sci 110 (Pt 9): 1091–1098, 1997Google Scholar
  152. 152.
    Deryugina EI, Bourdon MA, Reisfeld RA, Strongin A: Remodeling of collagen matrix by human tumor cells requires activation and cell surface association of matrix metalloproteinase-2. Cancer Res 58(16): 3743–3750, 1998Google Scholar
  153. 153.
    Nagase H: Cell surface activation of progelatinase A (proMMP-2) and cell migration. Cell Res 8(3): 179–186, 1998Google Scholar
  154. 154.
    Zuo J, Ferguson TA, Hernandez YJ, Stetler-Stevenson WG, Muir D: Neuronal matrix metalloproteinase-2 degrades and inactivates a neurite-inhibiting chondroitin sulfate proteoglycan. J Neurosci 18(14): 5203–5211, 1998Google Scholar
  155. 155.
    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, 1999Google Scholar
  156. 156.
    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, 1996Google Scholar
  157. 157.
    Hofmann UB, Westphal JR, Waas ET, Becker JC, Ruiter DJ, van Muijen GN: Co-expression of integrin alpha(v)beta3 and matrix metalloproteinase-2 (MMP-2) coincides with MMP-2 activation: correlation with melanoma progression. J Invest Dermatol 115(4): 625–632, 2000Google Scholar
  158. 158.
    Xue W, Mizukami I, Todd RF 3rd, Petty HR: Urokinasetype plasminogen activator receptors associate with beta1 and beta 3 integrins of fibrosarcoma cells: dependence on extracellular matrix components. Cancer Res 57(9): 1682–1689, 1997Google Scholar
  159. 159.
    Deryugina EI, Bourdon MA, Jungwirth K, Smith JW, Strongin AY: Functional activation of integrin alpha V beta 3 in tumor cells expressing membrane-type 1 matrix metalloproteinase. Int J Cancer 86(1): 15–23, 2000Google Scholar
  160. 160.
    Yan L, Moses MA, Huang S, Ingber DE: Adhesiondependent control of matrix metalloproteinase-2 activation in human capillary endothelial cells. J Cell Sci 113(Pt 22): 3979–3987, 2000Google Scholar
  161. 161.
    Deryugina EI, Ratnikov B, Monosov E, Postnova TI, DiScipio R, Smith JW, Strongin AY: MT1-MMP Initiates Activation of pro-MMP-2 and integrin alphavbeta3 Promotes Maturation ofMMP-2 in Breast Carcinoma Cells. Exp Cell Res 263(2): 209–223, 2001Google Scholar
  162. 162.
    Janat MF, Argraves WS, Liau G: Regulation of vascular smooth muscle cell integrin expression by transforming growth factor beta1 and by platelet-derived growth factor-BB. J Cell Physiol 151(3): 588–595, 1992Google Scholar
  163. 163.
    Tysnes BB, Haugland HK, Bjerkvig R: Epidermal growth factor and laminin receptors contribute to migratory and invasive properties of gliomas. Invasion Metastasis 17(5): 270–280, 1997Google Scholar
  164. 164.
    Yu X, Miyamoto S, Mekada E: Integrin alpha 2 beta 1-dependent EGF receptor activation at cell–cell contact sites. J Cell Sci 113(Pt 12): 2139–2147, 2000Google Scholar
  165. 165.
    Hotary K, Allen E, Punturieri A, Yana I, Weiss SJ: Regulation of cell invasion and morphogenesisin a threedimensional type I collagen matrix by membrane-type matrix metalloproteinases 1, 2, and 3. J Cell Biol 149(6): 1309–1323, 2000Google Scholar
  166. 166.
    Hauck CR, Hsia DA, Schlaepfer DD: Focal adhesion kinase facilitates platelet-derived growth factor-BB-stimulated ERK2 activation required for chemotaxis migration of vascular smooth muscle cells. J Biol Chem 275(52): 41092–41099, 2000Google Scholar
  167. 167.
    Troussard AA, Costello P, Yoganathan TN, Kumagai S, Roskelley CD, Dedhar S: The integrin linked kinase (ILK) induces an invasive phenotype via AP-1 transcription factor-dependent upregulation of matrix metalloproteinase 9 (MMP-9). Oncogene 19(48): 5444–5452, 2000Google Scholar
  168. 168.
    Yana I, Weiss SJ: Regulation of membrane type-1 matrix metalloproteinase activation by proprotein convertases. Mol Biol Cell 11(7): 2387–2401, 2000Google Scholar
  169. 169.
    Loechel F, Fox JW, Murphy G, Albrechtsen R, Wewer UM: ADAM 12-S cleaves IGFBP-3 and IGFBP-5 and is inhibited by TIMP-3. Biochem Biophys Res Commun 278(3): 511–515, 2000Google Scholar
  170. 170.
    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, 1999Google Scholar
  171. 171.
    Shalinsky DR, Brekken J, Zou H, McDermott CD, Forsyth P, Edwards D, Margosiak S, Bender S, Truitt G, Wood A, Varki NM, Appelt K: Broad antitumor and antiangiogenic activities ofAG3340, a potent and selectiveMMP inhibitor undergoing advanced oncology clinical trials. Ann NY Acad Sci 878: 236–270, 1999Google Scholar
  172. 172.
    Noha M, Yoshida D, Watanabe K, Teramoto A: Suppression of cell invasion on human malignant glioma cell lines by a novel matrix-metalloproteinase inhibitor SI-27: in vitro study. J Neuro-Oncol 48(3): 217–223, 2000Google Scholar

Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • Timothy E. VanMeter
    • 1
  • Harcharan K. Rooprai
    • 2
  • Mavis M. Kibble
    • 2
  • Helen L. Fillmore
    • 1
  • William C. Broaddus
    • 1
  • Geoffrey J. Pilkington
    • 2
  1. 1.Division of NeurosurgeryMedical College of Virgina-Virginia Commonwealth UniversityRichmondUSA
  2. 2.Experimental Neuro-oncology Group, Department of Neuropathology, Institute of PsychiatryKing's College LondonLondonUK

Personalised recommendations