EFFECTS OF DECIDUA-CONDITIONED MEDIUM AND INSULIN-LIKE-GROWTH-FACTOR BINDING PROTEIN-1 ON TROPHOBLASTIC MATRIX METALLOPROTEINASES AND THEIRINHIBITORS

The regulatory role of in vitro decidualized stromal cells (DESCM) and their main secretory product insulin-like growth factor binding prote in-1 (IGFBP-1) was studied on the secretion of trophoblastic gelatinas es and tissue inhibitor of metalloproteinase (TIMP-1). First trimester cytotrophoblastic cells (CTB) were obtained from abortions and cultur ed in vitro in presence or absence of DESCM or IGFBP-1. Secreted gelat inases were analysed in the culture supernatants by zymography and by measurements of the total gelatinolytic activity. TIMP-1, hCG, and fet al fibronectin (fFN) were measured by commercially available immunoass ays. DESCM inhibited the total gelatinolytic activity of CTB but incre ased trophoblastic MMP-9, TIMP-1 and fFN. In contrast, IGFBP-1 increas ed the total gelatinolytic activity and TIMP-1, had no effect on MMP-2 , MMP-9 or fFN but inhibited hCG. It is concluded that a factor secret ed by decidual cells inhibits the gelatinolytic property of trophoblas t by increasing TIMP-1. Other decidual factors, as yet unidentified, i ncrease MMP-2 and MMP-9 to an extent which does override the inhibitor y effect of TIMP-1. Since in contrast to DESCM, IGFBP-1 increases the total gelatinolytic activity of CTB, it cannot be the primary active d ecidual factor regulating the proteolytic activity of CTB. The possibi lity of an integrin-mediated effect of IGFBP-1 on CTB is discussed. (C ) 1998 W. B. Saunders Company Ltd.