Proliferation of human carcinoma cells in calcium-deficient culture medium may depend on autocrine growth factor(s)

The ability to proliferate in media with low calcium concentrations (less than 0.1 mM) at clonal seeding densities is a characteristic of malignant cells. Cells of the carcinoma line C-4I are an exception, and are unable to proliferate in medium with 0.02 mM calcium (LCM) when seeded at low densities. Conditioned medium, derived from a subline of C-4I cells that were adapted to grow in LCM, contained an acid-stable factor of greater than 8 kilodaltons molecular weight that mediated proliferation and colony formation of unadapted C-4I cells in LCM in a concentration-dependent manner. The effect was not related to enhanced cell attachment or spreading, and was maximal when the unadapted C-4I cells were seeded in aggregates of 2-20 cells rather than singly. Thus, calcium independence, a component of the neoplastic phenotype, may be mediated by autocrine tumor-cell-derived factor(s) and may involve long- and short-range cell interactions.