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 semi-solid medium, forming colonies ranging from tight, to loose, or dispersed. These phenotypes were found to be stable on cloning and retesting. Examination of the serum-free media conditioned by these clones indicates that the clones release activities capable of inducing agar colonies, in an indicator cell line (NRK, 49F), that express phenotypes similar to those of the melanoma clones used to produce the serum-free conditioned media (SF-CM). These SF-CM contained a transforming growth factor (TGF) beta (apparent Mr 14 700) and a single, apparently high Mr TGF-alpha species. Co-eluting with the TGF-alpha at an Mr of approximately 22 500 was a previously undescribed activity capable of modulating the phenotype of the NRK agar colonies induced by the combination of TFGs alpha and beta. This new activity can modulate the usual tight colony to express a loose or dispersed phenotype characteristic of the producer cells. The possible role these ectopic peptides play in the expression of the transformed phenotype by the tumour cells producing them, and the possible correlation between the 22 500 Mr EGF-like peptide (TGF-alpha) released by this particular tumour line and high Mr EGF-like peptides found in the urine of cancer patients, are both discussed.