A Diffusible Factor Restoring Contact Inhibition of Growth to Malignant Melanocytes

Abstract

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.

Vitiligo-related pigment cell differentiation antigens are expressed on malignant melanoma cells following phenotypic reversion induced by contact inhibitory factor

“…1; Table 1). In contrast, CIF-treated RPMI-1846 cells at 7 days displayed the characteristic morphologic changes previously described [7], with the formation of well-oriented monolayers of bipolar cells. Approximately 80% of these reverted cells now exhibited granular surface fluorescence for pigmentcell antigens ( Fig.…”

Improvement of the Tumor-Suppressive Effect of Boron Neutron Capture Therapy for Amelanotic Melanoma by Intratumoral Injection of the Tyrosinase Gene

“…We report here that two hamster amelanotic melanoma cell lines, D178 (17) and FF (18), had statistically significant increases in BPA uptake by the tumor tissues, and the tumor-suppressive effect in animals that had received an intratumor injection of the tyrosinase gene showed improvement.…”

“…Greene (17), was maintained in MEM with 10% fetal bovine serum (FBS). Hamster-derived FF amelanotic melanoma purchased from Dainippon Pharmaceutical Co., Ltd., Tokyo, Japan (18) was maintained in RPMI 1640 with 10% FBS.…”

The Plasma Unit Membrane.

“…Finally, recent investigations suggest that proteins in tissue extracts or serum are able to restore the altered surface properties of proliferating tumour cells. Protein containing extracts from melanocytes restored contact inhibition in malignant melanoma (Lipkin & Knecht, 1974), and Stankler (1976) reported that the serum of convalescent psoriatic patients contained a protein factor which prevented provocation of psoriasis.…”