title: The expression of PDGF alpha- and beta-receptors in subpopulations of PDGF-producing cells implicates autocrine stimulatory loops in the control of proliferation in cytotrophoblasts that have invaded the maternal endometrium.
abstract: In order to explain the high proliferative potential of human placental cytotrophoblasts, we have addressed the potential involvement of platelet-derived growth factor (PDGF) ligand and receptors. Although PDGF is usually described as a mitogen for cells of mesenchymal origin, we show in this report that extra-villous term placental cytotrophoblasts express the PDGF alpha- and beta-receptor genes, both in vivo and in vitro. In addition, cytotrophoblasts produce significant amounts of PDGF-B protein. By immunohistochemical analysis of receptor expression, we found that the PDGF alpha-receptors could be detected at the cell surface, while the PDGF beta-receptors were only detected intracellularly. In addition, double immunostaining analysis showed that the PDGF alpha- and beta-receptor molecules are expressed in different subpopulations of cytotrophoblasts. The addition of PDGF-AA and PDGF-BB homodimers to cytotrophoblast primary cultures induced a significant increase in DNA synthesis. We conclude, therefore, that PDGF is a growth factor for placental cytotrophoblasts and suggest that the growth of cytotrophoblasts can partly be explained by a PDGF autostimulatory loop, limited by the number of receptor-positive cytotrophoblasts.
authors.affiliation: Laboratory for Molecular Development and Tumour Biology, Institute of Experimental Drug Research, Karolinska Hospital, Stockholm, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Holmgren
authors.forename: L
authors.initials: L
authors.lastname: Claesson-Welsh
authors.forename: C H
authors.initials: CH
authors.lastname: Heldin
authors.forename: R
authors.initials: R
authors.lastname: Ohlsson
mesh_terms: D002462:Cell Membrane / Q000737:chemistry; D002478:Cells, Cultured; D004717:Endometrium / Q000166:cytology; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D006801:Humans; D010920:Placenta / Q000737:chemistry* / Q000166:cytology; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D011247:Pregnancy; D017479:Receptors, Platelet-Derived Growth Factor / Q000032:analysis* / Q000235:genetics; D014327:Trophoblasts / Q000737:chemistry
chemical_list: D010982:Platelet-Derived Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor