Cell locomotion and contact inhibition of normal and neoplastic rat cells.

Abstract

AbstractThe morphology, locomotion and contact inhibition of locomotion of normal and neoplastic rat cells were studied in relation to oncogenicity. Embryonic fibroblasts (LWF) and a spontaneously neoplastic variant (LW13) were both fibroblastic in appearance, with a monolayered arrangement of cells at moderate densities. A variant transformed by Rous sarcoma virus (RsK4) was epithelioid and was also well monolayered. Scanning electron microscopy revealed a smooth dorsal surface on LWF cells, microvilli on the dorsal surface of LW13 cells and numerous microvilli, blebs and ruffles over the entire surface of RsK4 cells. LWF cells and LW13 cells moved with broad fan‐shaped lamellae on which lamellipodia (ruffles) arose at the leading edge. These cells showed polarized locomotion and migrated rapidly into wounds made in confluent cultures. RsK4 cells neither possessed large, fan‐shaped lamellae nor showed polarized movement. They did not invade wounds efficiently. After treatment with colcemid LWF and LW13 cells resembled RsK4 cells more closely and lost polarity of movement. On analysis of cell collisions by time‐lapse cinemicrography, the three cell types showed pronounced homotypic contact inhibition of cell locomotion, as judged by cessation of forward displacement. LWF and LW13 cells exhibited paralysis of ruffling, contraction of the leading edge, cell to cell adhesion and inhibition of pinocytosis typical of contact inhibition between fibroblasts. Paralysis and contraction were not evident in RsK4 cell collisions. Colcemid treatment did not prevent the initiation of contact inhibition but reduced the lasting paralysis of LWF and LW13 cells. In collisions between tumour cells and normal cells, cell locomotion and membrane ruffling were inhibited in the normal cells but not in the tumour cells. Such non‐reciprocal contact inhibition resulted in apparent monolayering in mixed cultures. The loss of contact inhibitory responses of neoplastic cells to normal cells appears to be more closely related to oncogenicity than are homotypic contact inhibition and cellular morphology. The contact inhibitory stimuli of certain neoplastic cells differ from those of normal fibroblasts, and may be preserved by fixation with glutaraldehyde.