Basigin (murine EMMPRIN) stimulates matrix metalloproteinase production by fibroblasts.
Analysis of basigin-null mice has shown that basigin is involved in several important physiological processes including reproductive, immune, and neural activities (Igakura et al., 1998, Dev Biol 194:152-165). However, its molecular mechanism of action in these processes has not yet been established. Our objective here is to determine whether basigin has functional properties similar to its apparent human tumor cell homolog, EMMPRIN, i.e., the ability to stimulate matrix metalloproteinase (MMP) production in fibroblasts (Guo et al. 1997, J Biol Chem 272:24-27). Mouse cells express two major forms of basigin that differ in their degree of glycosylation (molecular weights: 45 and 58 kDa) but, in similar fashion to human EMMPRIN, mouse tumor cells express higher levels of basigin than normal cells. We have used three different methods to show that basigin stimulates MMP expression in fibroblasts. First, recombinant basigin was partially purified from transfected CHO cells by affinity chromatography. This basigin preparation stimulates production of MMPs on addition to fibroblasts in culture. Second, co-culture of basigin-transfected CHO cells with fibroblasts gives rise to increased expression of MMPs as compared to control co-cultures. Third, we employed a novel approach in which a recombinant basigin adenovirus was constructed and used to infect the target fibroblasts, so that mutual stimulation between neighboring fibroblasts would be expected to result. In this method also, basigin stimulates production of MMPs. Finally, we showed that addition of basigin or EMMPRIN antibody, respectively, to recombinant basigin or EMMPRIN adenovirus-infected cells augments stimulation of MMP synthesis, implying that cross-linking of basigin/EMMPRIN in the membrane enhances activity. We conclude that murine basigin and human EMMPRIN have similar MMP-inducing activities and are functional homologs.
Li
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Department of Anatomy and Cellular Biology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.
Huang
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Guo
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Toole
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D016475:3T3 Cells; D000818:Animals; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; D001483:Base Sequence; D051926:Basigin; D001798:Blood Proteins; D016466:CHO Cells; D002460:Cell Line; D018920:Coculture Techniques; D006224:Cricetinae; D017931:DNA Primers; D005347:Fibroblasts / Q000201:enzymology / Q000502:physiology; D006031:Glycosylation; D006801:Humans; D020782:Matrix Metalloproteinases / Q000235:genetics* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; C497886:BSG protein, human; D001798:Blood Proteins; C102624:Bsg protein, Gallus gallus; C497887:Bsg protein, mouse; C079432:Bsg protein, rat; D017931:DNA Primers; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D051926:Basigin; D020782:Matrix Metalloproteinases