EXPRESSION OF MEL-CAM IN IMPLANTATION SITE INTERMEDIATE TROPHOBLASTICCELL-LINE, IST-1, LIMITS ITS MIGRATION ON UTERINE SMOOTH-MUSCLE CELLS

An immortalized implantation site intermediate trophoblastic cell line , IST-1, was established from a human placenta of 7 weeks gestation. I ST-1 cells phenotypically resembled the implantation site intermediate trophoblastic cells in situ and expressed Mel-CAM (MUC 18 or CD146). Mel-CAM is a cell adhesion molecule belonging to the immunoglobulin ge ne superfamily, It is involved in heterophilic cell-cell adhesion and plays a role in several biological processes including tumor progressi on. We have previously shown that Mel-CAM was highly expressed in the intermediate (extravillous) trophoblast in the human implantation site . In this study we determined the function of Mel-CAM in the interacti on of trophoblast and uterine smooth muscle in the implantation site. IST-1 cells failed to adhere to immobilized recombinant Mel-CAM in sol id phase whereas the uterine smooth muscle cells did. The presence of the putative Mel-CAM ligand in smooth muscle cells was further support ed by the finding that Mel-CAM-transfected but not the mock-transfecte d U937 leukemia cells bind to the confluent monolayer of uterine smoot h muscle cells. IST-1 cells attached efficiently to the monolayer of t he uterine smooth muscle cells and acquired a spindle-shaped morpholog y simulating smooth muscle cells. The cell binding was only marginally affected by Mel-CAM blocking antibodies. However, Mel-CAM blocking an tibodies and recombinant Mel-CAM promoted cell migration from IST-1 ce ll spheroids on the smooth muscle monolayer, Taken together, our resul ts suggest that IST-1 cells express Mel-CAM but not the putative Mel-C AM ligand, In contrast, the uterine smooth muscle cells express the pu tative Mel-CAM ligand which binds to Mel-CAM on the surface of the IST -1 cells. The interaction between Mel-CAM and its putative ligand conf ers a stationary phenotype for trophoblastic cells. These observations are consistent with an important role for Mel-CAM in limiting trophob lastic migration within the myometrium in the implantation site.