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.
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.
Holmgren
L
L
Laboratory for Molecular Development and Tumour Biology, Institute of Experimental Drug Research, Karolinska Hospital, Stockholm, Sweden.
Claesson-Welsh
L
L
Heldin
C H
CH
Ohlsson
R
R
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
D010982:Platelet-Derived Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor