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Association of Increased Platelet-derived Growth Factor Secretion and Retroviral Expression in Transformed Mouse and Human Cells¹

Department of Pathology, University of Washington, Seattle, Washington 98195

The activation of platelet-derived growth factor (PDGF) production by transformed cells is often observed but not well understood. We have examined cell lines that showed "spontaneous" increases in PDGF secretion, i.e., in which the increase was not in response to intentional intervention. In one case the increase was associated with an obvious change in morphology and mitogen requirements accompanying spontaneous transformation of Swiss 3T3 cells. In the other case the increase occurred during growth of a human tumor cell in a nude mouse and was not associated with an alteration in the morphology or growth properties of the cells. Rates of PDGF secretion did not correlate with specific changes in the pattern of expression of PDGF mRNA. In the human tumor system PDGF A- and B-chain transcripts were present at similar levels before and after transplantation in the nude mouse. In the 3T3 cell system, B-chain transcripts were detected only after transformation, and there was no change in the low basal expression of A-chain. A change which did consistently correlate with the increased secretion of PDGF was that both the spontaneously transformed murine cells and the transplanted human cells expressed murine leukemia virus transcripts and synthesized retroviral envelope glycoproteins, while their original counterparts did not.

¹ This research was supported by NIH Grants GM35501 and CA28238 and by a grant from the Life and Health Insurance Medical Research Fund.

² Present address: Research Institute, Genetics Dept., Hospital for Sick Children, 555 University Ave., Toronto, Ontario, Canada M5G1X8.

³ To whom requests for reprints should be addressed.

⁴ Present address: Dept. of Pathology, St. Louis University Medical Center, 104 S. Grand Blvd., St. Louis, MO 63104.

Received 12/16/87. Revised 5/18/88. Accepted 5/27/88.