Differentiation-dependent production of a platelet-derived growth factor-like mitoattractant by endoderm cells derived from embryonal carcinoma cells

Abstract

Retinoic acid-induced differentiation of F9 embryonal carcinoma cells to endoderm provokes the secretion of a protein factor that acts as both a chemoattractant and mitogen for smooth muscle cells. Undifferentiated F9 cells and PSA-5E (visceral endodermlike) cells produced little of this factor. However, PYS-2 (parietal endodermlike) and Dif 5 endoderm cells were found to produce significant amounts of endoderm-derived mitoattractant (EDM) activity. The activity secreted by the Dif 5 cells was partially purified using gel filtration chromatography using chemotaxis and mitogenic assays as markers for biological activity. The partially purified activity competes with [125I]iodo-platelet-derived growth factor (PDGF) for binding to target cells, and the biological activity is neutralized with anti-PDGF IgG, suggesting shared domains in the two molecules. However, the factor appears to be different from PDGF, based on its thermal stability, molecular weight, and charge. The differentiated endoderm cells including retinoic acid (RA)-treated F9, Dif 5, PSA-5E, and PYS-2 cells also exhibit specific [125I]iodo-PDGF binding, and the PSA-5E cells respond to PDGF as a chemoattractant. Conceivably, such a PDGF-like factor may contribute to the regulation of cell growth and migration during the early stages of embryogenesis.