Expression of Mel-CAM in implantation site intermediate trophoblastic cell 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. IST-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 gene superfamily. It is involved in heterophilic cell-cell adhesion and plays a role in several biological processes including tumor progression. 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 interaction of trophoblast and uterine smooth muscle in the implantation site. IST-1 cells failed to adhere to immobilized recombinant Mel-CAM in solid phase whereas the uterine smooth muscle cells did. The presence of the putative Mel-CAM ligand in smooth muscle cells was further supported by the finding that Mel-CAM-transfected but not the mock-transfected U937 leukemia cells bind to the confluent monolayer of uterine smooth muscle cells. IST-1 cells attached efficiently to the monolayer of the uterine smooth muscle cells and acquired a spindle-shaped morphology simulating smooth muscle cells. The cell binding was only marginally affected by Mel-CAM blocking antibodies. However, Mel-CAM blocking antibodies and recombinant Mel-CAM promoted cell migration from IST-1 cell spheroids on the smooth muscle monolayer. Taken together, our results suggest that IST-1 cells express Mel-CAM but not the putative Mel-CAM ligand. In contrast, the uterine smooth muscle cells express the putative 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 confers a stationary phenotype for trophoblastic cells. These observations are consistent with an important role for Mel-CAM in limiting trophoblastic migration within the myometrium in the implantation site.
Department of Pathology, the Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. ishih@welchlink.welch.jhu.edu
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Shih
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Wang
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Wu
R J
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Kurman
J D
JD
Gearhart
D000818:Animals; D015703:Antigens, CD; D000954:Antigens, Surface / Q000096:biosynthesis* / Q000502:physiology*; D051929:CD146 Antigen; D002448:Cell Adhesion / Q000502:physiology; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000502:physiology*; D018920:Coculture Techniques; D047108:Embryonic Development / Q000502:physiology; D005260:Female; D006801:Humans; D008024:Ligands; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000502:physiology*; D051379:Mice; D016513:Mice, SCID; D009130:Muscle, Smooth / Q000166:cytology* / Q000502:physiology; D019006:Neural Cell Adhesion Molecules; D010641:Phenotype; D011247:Pregnancy; D014327:Trophoblasts / Q000166:cytology / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014599:Uterus / Q000166:cytology*
D015703:Antigens, CD; D000954:Antigens, Surface; D051929:CD146 Antigen; D008024:Ligands; C497902:MCAM protein, human; C497903:Mcam protein, mouse; D008562:Membrane Glycoproteins; D019006:Neural Cell Adhesion Molecules