Ectopic peptides released by a human melanoma cell line that modulate the transformed phenotype

Cells derived from a human melanoma strain by low-serum selection in monolayer were found to be capable of growth in semisolid medium, forming colonies ranging from tight to loose or dispersed. These phenotypes were found to be stable after cloning and retesting. Examination of the biological activities of ectopic peptides produced by a clone that gives rise to loose dispersed colonies revealed the presence of a transforming growth factor beta (TGF-beta; apparent Mr 14,700) and a single TGF-alpha species produced at an unusually high concentration (2.2 ng/ml). Coeluted with the TGF-alpha at approximately 22,500 was a mitogenic activity and a previously undescribed activity capable of modulating the phenotype of induced normal rat kidney fibroblast (NRK-49F) colonies in semisolid medium. This activity can modulate the usual tight colony to express a loose or dispersed phenotype characteristic of the producer cells. Both the possible role these ectopic peptides play in the expression of the transformed phenotype by the tumor cells producing them and the possible correlation between the Mr 22,500 epidermal growth factor-like peptide released by this particular tumor line and high molecular weight epidermal growth factor-like peptides found in the urine of cancer patients are discussed.