Autocrine growth factors for human tumor clonogenic cells

Abstract

A human epithelial-derived cell line, SW-13, releases a soluble substance that functions as an autocrine growth factor. SW-13 cells, derived from a human adenocarcinoma of the adrenal cortex, form a few small colonies when suspended in soft agar at low densities. The number of colonies increased significantly when either viable SW-13 cells or serum-free medium conditioned by SW-13 cells (CM) was added to agar underlayers. CM increased colony formation in a dose-dependent fashion. Clonal growth at low cell densities was dependent on the presence of both horse serum and SW-13 CM. Neither activity alone was capable of sustaining growth. Even when cells were plated at high densities CM could not substitute for serum, but could reduce the threshold serum concentration. The results suggest that autocrine and serum-derived factors act in concert to maintain clonal growth of epithelial tumor cells in soft agar.

Enhancement of anchorage‐independent growth of a human adrenal carcinoma cell line by endogenously produced basic fibroblast growth factor

“…Previous studies from several laboratories (Halper and Moses, 1983;Hamburger and White, 1985) have demonstrated that SW-13 adrenal carcinoma cells produce factors that enhance clonal growth of this cell line in soft agar. We now provide evidence that much of the autocrine activity present in cell lysates is due to production of a mitogen indistinguishable from bFGF as judged by several criteria.…”

“…Protein concentration was determined as described by Bradford ( 1976). ated as described by Hamburger and White (1985). Onemilliliter base layers of 0.5% agar (Difco, Detroit, MI) containing enriched McCoy's 5A medium were prepared in sterile plastic 35-mm Petri dishes.…”

“…Previous work from our laboratory (Hamburger and White, 1985) and that of Halper and Moses (1983) have indicated that purified basic FGF at picomolar concentrations enhances anchorage-independent growth of SW-I 3 cells. The possibility that the colony-stimulating activity present in SW-13 cells was due to bFGF was further examined.…”

“…The ability of SW-13 lysates and conditioned medium to stimulate growth of SW-13 cells plated at low clonal densities supports an autocrine model of cell growth (Halper and Moses, 1983;Hamburger and White, 1985). The identity of the active factors in SW-13 lysates has not been established.…”

Differences in Growth Factor Sensitivity between Primary and Transformed Murine Cell Cultures Revealed by BrdU/Hoechst Flow Cytometry

“…Their greater sensitivity could result from increased numbers of cell surface receptors and/or amplification of any of the various signal transduction path ways. In this sense, the acquisition of en hanced growth factor sensitivity would cor respond to a first step in the direction of an autocrine mechanism of growth control [4,5,18,19]. The transformed cells display their greatest sensitivity at low serum con centrations.…”