A cell line was derived from a metastatic, human melanoma. It is producing peptides that can stimulate an untrasformed cell line to reversibly express a transformed phenotype. This transformed phenotype is expressed in monolayers of untransformed cells as a disorganized growth pattern and in anchorage-independent growth (AIG) assays as colonies forming in soft-agar from single seeded cells. One of the peptides in this mixture contributing to this activity is an epidermal growth factor-like growth factor that has a molecular weight of approximately 24,000 daltons as determined by gel permeation chromatography on Bio-Gel P-30 in 1 M acetic acid. This appears to be present at high concentrations (2.5 g/liter). The mitogenic activity present in these fractions coelutes with the EGF-like activity. Two additional activities are eluted from the Bio-Gel column. The first of these coelutes with the EGF-like activity and appears to mitigate cell cell interactions, both in the cells of induced agar colonies and in monolayers of NRK cells. The last activity eluting from the column is a TGF-beta. This TGF-beta activity has an apparent molecualar weight of approximately 14,500 daltons. These """"""""ectopic"""""""" peptides may play a role in the expression of the transformed phenotype of the tumor cells producing them. Molecular clones have been derived from sequences regulated by the combination of EGF and TGF-beta. The identification of these induced sequences wil, hopefully, add to understanding of the role of these factors in the expression of the transformed state.
