Current treatments of many advanced malignancies, including melanoma, have failed to significantly reduce mortality rates, necessitating newer approaches. There is now abundant evidence that cancer cells, given the appropriate environmental and molecular context, are capable of remarkable plasticity, including complete reversal of the malignant phenotype. Such reprogramming involves both extrinsic and intrinsic factors and can occur via three routes: perturbations of extracellular matrix-cell receptor interactions, modulation of intracellular signaling pathways, and exploitation of epigenetic inheritance. Studies demonstrate the potential for producing dramatic changes in structural, biochemical, immunological, and functional properties of a broad spectrum of tumor cell types, including melanoma, leading to growth arrest, differentiation, senescence, or self destruction. Translating the promise inherent in tumor cell plasticity to the clinical arena remains a major challenge, but it is likely that a variety of epigenetic methods will play an increasingly important and effective role in the future control of malignant melanoma and other cancers.
Contact inhibition of growth is the property in vitro whose loss is most closely correlated with tumorigenicity in vivo. A contact-inhibited melanocytic cell line produces a diffusible protein-containing factor capable of restoring contact inhibition of cell division to highly malignant hamster melanocytes. Its addition to subconfluent cultures of the malignant cells is followed by the obligatory acquisition, at confluence, of the contact-inhibited state. Cultures are flat, oriented, and fibroblastlike, and show a 55% decrease in saturation density with no loss of viability. The effect is reversible. Present in conditioned media of cultures of the contact-inhibited melanocytic cell line, isolated by column chromatography on Sephadex G-200, the factor appears to be of high molecular weight. Activity is preserved in aqueous solutions at 40 for at least 8 weeks, but is destroyed by repeated freezethawing or by treatment with Pronase.This newly recognized contact-inhibitory factor may be a prototype for a more general and fundamental mechanism for regulation of normal cell-cell interactions. It is the first cell-elaborated factor to be isolated that is capable of restoring the capacity for contact inhibition of growth to malignant cells.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.