AUTOINDUCTION OF PLATELET-DERIVED GROWTH-FACTOR (PDGF) A-CHAIN MESSENGER-RNA EXPRESSION IN A HUMAN-MALIGNANT MELANOMA CELL-LINE AND GROWTH-INHIBITORY EFFECTS OF PDGF-A-CHAIN MESSENGER RNA-SPECIFIC ANTISENSE MOLECULES

Autoinduction of PDGF-A-chain mRNA's was demonstrated in cells of a human malignant melanoma cell line (HTZ 19), indicating a PDGF-induced amplification of an autocrine growth factor loop mechanism. PDGF-alpha receptors were detected by immunocytochemistry in HTZ 19 melanoma cells. Exogenously administered PDGF-AA exerted an increase in cell proliferation by 70% at 200 ng/ml PDGF in serum-supplemented cell culture medium. Antisense phosphorothioate-oligodeoxynucleotides (S-ODN's), specifically targeted against PDGF-A-chain mRNA, reduced cell proliferation of HTZ 19 melanoma cells by 62% at a concentration of 5.0 μM, also only in serum-enriched medium. These findings strongly suggest that PDGF-AA homodimers may be an autocrine growth factor for HTZ 19 melanoma cells but require synergistic interaction with serum components. © 1993 Academic Press, Inc.