Cellular specificity of fibroblastic proMMP-3 downregulation by normal or cancer trophoblastic cells

It has been shown previously that endometrial fibroblast prometalloproteinase-3 (proMMP-3) secretion is inhibited by normal cytotrophoblasts as a result of paracrine interactions. To investigate the specificity of this downregulation, two different types of co-culture were used. First, peritoneal and synovial fibroblasts obtained from human tissue biopsies were co-cultured with normal cytotrophoblasts. By contrast to what has been observed with endometrial fibroblasts, their proMMP-3 secretion increased though their morphology was slightly modified. Secondly, the regulation of endometrial proMMP-3 secretion was tested in co-cultures with two choriocarcinoma cell lines (JAr and JEG-3 cell lines). With tumoral cytotrophoblastic cells, endometrial fibroblasts became decidua-like cells and JAr and JEG-3 cell lines grew in syncytium. However, co-culture of endometrial fibroblasts with JAr and JEG-3 choriocarcinoma cells did not decrease proMMP-3 secretion. The present results show that endometrial proMMP-3 downregulation is tissue specific and does not depend on cell differentiation. A cytotrophoblast cell membrane factor which might not be expressed in tumoral cells could probably play a role in paracrine relations between epithelial cells and surrounding stroma.