Basigin (murine EMMPRIN) stimulates matrix metalloproteinase production byfibroblasts

Analysis of basigin-null mice has shown that basigin is involved in several important physiological processes including reproductive, immune, and neur al activities (lgakura et al., 1998, Dev Biol 194:152-165). However, its mo lecular mechanism of action in these processes has not yet been established . Our objective here is to determine whether basigin has functional propert ies similar to its apparent human tumor cell homolog, EMMPRIN, i.e., the ab ility to stimulate matrix metalloproteinase (MMP) production in fibroblasts (Guo et al. 1997, j Biol Chem 272:24-27). Mouse cells express two major fo rms of basigin that differ in their degree of glycosylation (molecular weig hts: 45 and 58 kDa) but, in similar fashion to human EMMPRIN, mouse tumor c ells express higher levels of basigin than normal cells. We have used three different methods to show that basigin stimulates MMP expression in fibrob lasts. First, recombinant basigin was partially purified from transfected C HO cells by affinity chromatography. This basigin preparation stimulates pr oduction of MMPs on addition to fibroblasts in culture. Second, co-culture of basigin-transfected CHO cells with fibroblasts gives rise to increased e xpression of MMPs as compared to control co-cultures. Third, we employed a novel approach in which a recombinant basigin adenovirus was constructed an d 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 EMMPRI N adenovirus-infected cells augments stimulation of MMP synthesis, implying that cross-linking of basigin/EMMPRIN in the membrane enhances activity. W e conclude that murine basigin and human EMMPRIN have similar MMP-inducing activities and are functional homologs. (C) 2001 Wiley-Liss, Inc.