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.
Extracellular matrix metalloproteinase inducer (EMMPRIN) also called CD147, basigin or M6 in the human is a member of the immunoglobulin superfamily that is enriched on the surface of tumor cells and stimulates adjacent stromal cells to produce several matrix metalloproteinases (MMPs). In this study, we have demonstrated that coculturing of EMMPRIN-expressing human glioblastoma multiforme cells (U251) with brain-derived human fibroblasts not only stimulates production, but also activation of pro-gelatinase A (proMMP-2), an enzyme that is enriched in malignant gliomas and most likely crucial to tumor progression. Production of membrane types 1 and 2-MMPs (MT1-MMP and MT2-MMP), which are activators of proMMP-2, was also stimulated in these cocultures. Stimulation of MMP-2, MT1-MMP and MT2-MMP production was inhibited by anti-EMMPRIN monoclonal antibody in a dose-dependent manner. Thus, we have shown, for the first time, that EMMPRIN causes increased expression of MT1-MMP and MT2-MMP, as well as increased production and activation of MMP-2.
Sameshima
T
T
Department of Neurosurgery, Miyazaki Medical College, 5200 Kihara, Kiyotake, 889-1692, Miyazaki, Japan. tetsuro@post1.miyazaki-med.ac.jp
Nabeshima
K
K
Toole
B P
BP
Yokogami
K
K
Okada
Y
Y
Goya
T
T
Koono
M
M
Wakisaka
S
S
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; D051926:Basigin; D001798:Blood Proteins; D001921:Brain / Q000166:cytology; D001932:Brain Neoplasms / Q000201:enzymology*; D018929:Cell Culture Techniques; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004790:Enzyme Induction; D005347:Fibroblasts / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000201:enzymology*; D006801:Humans; D053517:Matrix Metalloproteinase 15; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000096:biosynthesis / Q000378:metabolism*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; C497886:BSG protein, human; D001798:Blood Proteins; C102624:Bsg protein, Gallus gallus; C079432:Bsg protein, rat; C507098:MMP15 protein, human; D008562:Membrane Glycoproteins; D051926:Basigin; D053517:Matrix Metalloproteinase 15; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2