AUTOCRINE GROWTH-REGULATION IN NEUROECTODERMAL TUMORS AS DETECTED WITH OLIGODEOXYNUCLEOTIDE ANTISENSE MOLECULES

THE CELL LINES of three neuroectodermal tumors, two glioblastomas (HTZ -146, HTZ-17) and one melanoma (HTZ-19) were established and screened for the expression of growth factors by northern blotting and immunoch emical methods. All three tumors were positive for platelet-derived gr owth factor- (PDGF-) A-, -B-chain, and basic fibroblast growth factor (bFGF) messenger ribonucleic acids. Cultured cells as well as original tumor material were also positive for PDGF-AA-, PDGF-BB, and bFGF pro tein, as shown by immunochemistry. To investigate the possible pathoph ysiological role of PDGF and bFGF, antisense technology was employed w ith chemically modified nuclease-stable 14-mer phosphorothioate oligod eoxynucleotides. Proliferation of all three tumors was reduced to a di fferent extent with antisense phosphorothioate oligodeoxynucleotides i n vitro, targeted against PDGF-A-chain-, B-chain-, and -bFGF-messenger ribonucleic acid. These data indicate autocrine stimulatory loops for PDGF and bFGF, which may be blocked, may have different relevance in neuroectodermal tumors in vitro, and may have conceivable future thera peutic implications.