Protease resistance of transformed cells in culture: production of growth-promoting factor(s) by protease-resistant cells.

The protease-resistant character of malignantly transformed cells was studied. Surface labeling experiments revealed that the cell surface of transformed cells treated with, or grown in the presence of a neutral protease (Dispase) was drastically altered by proteolytic digestion, and showed that transformed cells could be stripped of many of their cell surface components without losing cell viability and growth ability. The protease-resistant character depended upon the degree of cell-crowding and was not expressed unless transformed cells were seeded at a high cell density, suggesting that some conditioning factor(s) contributes to its expression. The protease-resistant cells (K-N7-8) could proliferate in serum-free, chemically defined medium and secreted growth-promoting factor(s) that allowed serum-free propagation of 3T3 cells (protease-sensitive cells). The test for protease resistance was presumed to discriminate between growth factor-secreting and non-secreting transformed cells. The ability of transformed cells to produce the growth factors that they need for continuous multiplication may be one of the mechanisms by which malignant cells escape from host growth control and become able to grow autonomously.