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Tumor Biology |
Departments of Oncology (S.A.R., H.M.), Clinical Neurosciences (S.A.R., H.M., P.A.F.), Medical Biochemistry (R.N.J.), and Pediatrics (P.A.F.), The University of Calgary, Calgary, Alberta, Canada T2N 4N1; Department of Pathology, Foothills Hospital, Calgary, Alberta, Canada, T2N 2T9 (N.B.R.); School of Biological Sciences, University of East Anglia, Norwich, Norfolk, England NR4 7TJ (D.R.E.); and the Department of Medicine, Tom Baker Cancer Centre, Calgary, Alberta, Canada T2N 4N2 (P.A.F.)
1 Address correspondence and reprint requests to Peter Forsyth, Tom Baker Cancer Centre, 1331 29th St. N.W., Calgary, Alberta, Canada.
Abstract
Malignant gliomas maintain a poor prognosis and survival rate due to their marked local invasive growth and neovascularization. Matrix metalloproteinases (MMPs) have been implicated in glioma invasion and angiogenesis, but it is unknown whether they are produced by the tumor cells or surrounding stroma. Using in situ hybridization and immunohistochemistry, we found expression of mRNA for both gelatinase-A (MMP2) and gelatinase-B (MMP9) localized to tumor cells and vascular structures in glioma sections. Gelatinase-A protein expression was detected most prominently in tumor cells, with very little signal seen in vasculature. Gelatinase-B protein expression was prominent in vascular structures but was also expressed in tumor cells. Our data show that these proteases are produced by glioma cells and vascular structures and suggest that synthetic MMP inhibitors might be useful in this disease.
References
Ashida, K., Nakatsukasa, H., Higashi, T., Ohguchi, S., Hino, N., Nouso, K., Urabe, Y., Yoshida, K., Kinugasa, N., and Tsuji, T. (1996) Cellular distribution of 92-kd type IV collagenase/gelatinase B in human hapatocellular carcinoma. Am. J. Pathol. 149,1803 -1811.[Abstract]
Aznavoorian, S., Murphy, A.N., Stetler-Stevenson, W.G., and Liotta, L.A. (1993) Molecular aspects of tumor cell invasion and metastasis. Cancer 71,1368 -1383.[CrossRef][Web of Science][Medline]
Costello, P.C., Del Maestro, R.F., and Stetler-Stevenson, W.G. (1994) Gelatinase A expression in human malignant gliomas. Ann. N. Y. Acad. Sci. 732,450 -452.[Web of Science][Medline]
Forsyth, P.A., Laing, T.D., Gibson, A.W., Rewcastle, N.B., Brasher, P., Sutherland, G., Johnston, R.N., and Edwards, D.R. (1998) High levels of gelatinase-B and active gelatinase-A in metastatic glioblastoma. J. Neurooncol. 36,21 -29.[CrossRef][Medline]
Forsyth, P.A., Wong, H., Laing, T.D., Rewcastle, N.B., Morris, D.G., Muzik, H., Leco, K.J., Johnston, R.N., Brasher, P.M.A., Sutherland, G., and Edwards, D.R. (1999) 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. Br. J. Cancer 79,1828 -1835.[CrossRef][Web of Science][Medline]
Giese, A., and Westphal, M. (1996) Glioma invasion in the central nervous system. Neurosurgery 39,235 -252.[CrossRef][Web of Science][Medline]
Harvey, M.B., Leco, K.J., Arcellana-Panlilio, M.Y., Zhang, X., Edwards, D.R., and Schultz, G.A. (1995) Proteinase expression in early mouse embryos is regulated by leukaemia inhibitory factor and epidermal growth factor. Development 121,1005 -1014.[Abstract]
Heppner, K.J., Matrisian, L.M., Jensen, R.A., and Rodgers, W.H. (1996) Expression of most matrix metalloproteinase family members in breast cancer represents a tumor-induced host response. Am. J. Pathol. 149,273 -282.[Abstract]
Kelly, P.J., Daumas-Duport, C., Scheithauer, B.W., Kall, B.A., and Kispert, D.B. (1987) Stereotactic histologic correlations of computed tomography- and magnetic resonance imaging-defined abnormalities in patients with glial neoplasms. Mayo Clinic Proc. 62,450 -459.[Web of Science][Medline]
Leco, K.J., Apte, S.S., Taniguchi, G.T., Hawkes, S.P., Khokha, R., Schultz, G.A., and Edwards, D.R. (1997) Murine tissue inhibitor of metalloproteinases-4 (TIMP-4): cDNA isolation and expression in adult mouse tissues. FEBS Lett. 401,213 -217.[CrossRef][Web of Science][Medline]
Nakagawa, T., Kubota, T., Kabuto, M., Fujimoto, N., and Okada, Y. (1996) Secretion of matrix metalloproteinase-2 (72 kD gelatinase/type IV collagenase = gelatinase A) by malignant human glioma cell lines: Implications for the growth and cellular invasion of the extracellular matrix. J. Neurooncol. 28, 13-24.[CrossRef][Medline]
Nakano, A., Tani, E., Miyazaki, K., Yamamoto, Y., and Furuyama, J. (1995) Matrix metalloproteinases and tissue inhibitors of metalloproteinases in human gliomas. J. Neurosurg. 83,298 -307.[Web of Science][Medline]
Nielsen, B.S., Sehested, M., Kjeldsen, L., Borregaard, N., Rygaard, J., and Dano, K. (1997) Expression of matrix metalloprotease-9 in vascular pericytes in human breast cancer. Lab. Invest. 77,345 -355.[Web of Science][Medline]
Rao, J.S., Steck, P.A., Mohanam, S., Stetler-Stevenson, W.G.,
Liotta, L.A., and Sawaya, R. (1993) Elevated levels of M(r)
92,000 type IV collagenase in human brain tumors. Cancer
Res. 53,2208
-2211.
Rao, J.S., Yamamoto, M., Mohaman, S., Gokaslan, Z.L., Stetler-Stevenson, W.G., Rao, V.H., Liotta, L.A., Nicolson, G.L., and Sawaya, R.E. (1996) Expression and localization of 92 kDa type IV collagenase/gelatinase B (MMP-9) in human gliomas. Clin. Exp. Metastasis 14,12 -18.[CrossRef][Web of Science][Medline]
Rutka, J.T., Matsuzawa, K., Hubbard, S.L., Fukuyama, K., Becker, L.E., Stetler-Stevenson, W., Edwards, D.R., and Dirks, P.B. (1995) Expression of TIMP-1, TIMP-2, 72- and 92-kDa type IV collagenase transcripts in human astrocytoma cell lines: Correlation with astrocytoma cell invasiveness. Int. J. Oncol. 6, 877-884.
Sawaya, R.E., Yamamoto, M., Gokaslan, Z.L., Wang, S.W., Mohanam, S., Fuller, G.N., McCutcheon, I.E., Stetler-Stevenson, W.G., Nicolson, G.L., and Rao, J.S. (1996) Expression and localization of 72 kDa type IV collagenase (MMP-2) in human malignant gliomas in vivo. Clin. Exp. Metastasis 14,35 -42.[Web of Science][Medline]
Uhm, J.H., Dooley, N.P., Villemure, J.-G., and Yong, V.W. (1996) Glioma invasion in vitro: Regulation by matrix metalloproteinase-2 and protein kinase C. Clin. Exp. Metastasis 14,421 -433.[CrossRef][Web of Science][Medline]
Woessner, J.F., Jr. (1991) Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J. 5,2145 -2154.[Abstract]
Wong, H., Anderson, W.D., Cheng, T., and Riabowol, K.T. (1994) Monitoring mRNA expression by polymerase chain reaction: The "primer-dropping" method. Anal. Biochem. 223,251 -258.[CrossRef][Web of Science][Medline]
Zedenius, J., Stahle-Backdahl, M., Enberg, U., Grimelius, L., Larsson, C., Wallin, G., and Backdahl, M. (1996) Stromal fibroblasts adjacent to invasive thyroid tumors: Expression of gelatinase A but not stromelysin 3 mRNA. World J. Surg. 20,101 -106.[CrossRef][Web of Science][Medline]
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