Modulation of survival and proliferation of BSC-1 cells through changes in spreading behavior caused by the tumor-promoting phorbol ester TPA.

Abstract

ABSTRACT. The effect of a tumor-promoting phorbol ester on spreading behavior was investigated to clarify the involvement of the interactions between cells and substratum in the maintenance of cell viability and the control of cell proliferation. BSC-1 cells did not spread and lost cell viability after a 24-h incubation in the absence of calf serum. Addition of calf serum initially induced radial spreading and then polarized spreading, with the formation on stress fibers and focal contact-like structure, and enhanced survival. Vitronectin also induced both radial spreading and polarized spreading, and enhanced cell survival. 12-O-Tetradecanoylphorbol-13-acetate (TPA) induced radial spreading with actin ribbons in the absence of serum. It improved the survival of cells attached to the substratum, but not in suspension. TPA suppressed polarized spreading, formation of stress fibers and of focal contact-like structure, and cell proliferation, in the presence of serum. Phorbol did not have any effect. These results suggest that enhancement of radial spreading and inhibition of polarized spreading of BSC-1 cells by TPA are closely related to the enhancement of cell survival and inhibition of cell growth.Interactions between cells and the substratum play a crucial role in the stimulative effects of serum on survival and growth of many lines of cultured cells (5,8,11,14,26). Serum contains various factors, such as spreading factors and growth factors, that are responsible for the potentiation of survival and growth of cultured cells. Adhesion of the cells to an adequate substratum is necessary for their growth in the presence of the serum (28). In contrast, certain substrata, such as type I collagen, suppress proliferation of BSC-1 cells (a continuous line of kidney cells derived from the African green monkey), while type IV collagen promotes the survival of BSC-1 cells in the absence of calf serum (25). It remains unclear how cell adhesion modulates the proliferation and survival of cells.Many studies using interference reflection microscopy have indicated that there are two types of adhesion of cells to the substratum (15, 16): focal contact and close contact. Focal contacts of fibroblasts with the substratum are considered to be closely associated with the functions of fibronectin and actin filaments (1, 2, 7, 10 , 27). Extracellular deposits of fibronectin are observed around the focal contacts (13,27). The close contacts seem to play a role in the regulation of cell motility (15 , 16).