Release from density-dependent inhibition of growth in the absence of cell locomotion

Thrombin may stimulate the proliferation of resting fibroblasts by itself or by potentiating the mitogenic effects of other growth stimulating agents. When added alone to a dense quiescent culture of chick embryo fibroblasts in either a serum-free or a low serum medium, thrombin stimulates these cells to proliferation a t a rate comparable to that seen with 5% serum. In the case of rabbit corneal fibroblasts neither fibroblast growth factor nor thrombin is particularly effective as a growth stimulant when added alone but exhibited a pronounced synergism on cell proliferation when present together. Established cell lines in the resting state, including 3T3, SV-3T3, 3T6, BHK-21 and 3T3 injected with avian sarcoma virus strain B77 (B77-3T3), are not responsive to thrombin alone. When the serum concentration in the medium equals or exceeds 2%, thrombin potentiates the mitogenic response of 3T3 cells to serum factors. With the exception of 3T3 and SV3T3 cells, the other cell lines show a potentiation of growth when thrombin is added to a low-serum (0.5%) medium containing epidermal growth factor and prostaglandin Fzu. The addition of thrombin to cultures of B77-3T3 cells growing in the presence of epidermal growth factor and prostaglandin Fza does not increase the initial growth rate of these cells but increases significantly the final cell density of these cultures.

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Thrombin potentiates the mitogenic response of cultured fibroblasts to serum and other growth promoting agents

Zetter

Sun

Chen

et al. 1977

Journal Cellular Physiology

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Epidermal growth factor induced membrane changes in 3T3 cells

Aharonov

Vlodavsky

Pruss

et al. 1978

Journal Cellular Physiology

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Epidermal growth factor (EGF) is a mitogen for Swiss 3T3 cells. Short incubation periods with physiological concentrations of EGF induced increased binding of Swiss 3T3 cells to Con A-coated nylon fibers. This effect was not induced in an EGF non-responsive 33 variant, in the transformed murine XC cells or in Swiss SV3T3 cells. The increase in Con A fiber-binding seems to be specific for EGF, since it was not observed in response to insulin, prostaglandin F2alpha or a higher serum concentration, which also initiate cell devision of confluent quiescent 3T3 cells. EGF also reduced Con A-mediated hemadsorption to 3T3, but had no effect on hemadsorption by the EFG non-responsive 3T3 variant. There was no change in the number of Con A-receptors on 3T3 cells after EGF treatment. Binding to WGA-coated fibers and WGA-mediated hemadsorption were not effected by preincubation with EGF.

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Effects of cytoskeletal disrupting agents on replication of bovine endothelium

Selden

Rabinovitch

Schwartz

1981

Journal Cellular Physiology

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Colchicine and vinblastine inhibited endothelial cell migration but had no effect on the stimulation of replication seen at wound edges in cultures of endothelium at stationary density. This is in contrast to the effects of cytochalasins which inhibit both migration and replication at wound edges. Moreover, colchicine and vinblastine stimulated cell replication in the unwounded, confluent monolayer. This effect has kinetics similar to the stimulation of replication at a wound edge and is associated with an initial retraction of cell borders, leaving gaps between cells. Cytochalasin D inhibited the growth response to microtubule disrupting agents but did not prevent cell retraction. Stimulation of replication by microtubule disrupting agents was not dependent on serum but was synergistic with serum in cultures rinsed repeatedly with serum-free medium. The replication occurred prior to any cell loss. When, however, cells were allowed to complete mitosis, about one-half of the daughter cells detached from the monolayer so that there was no increase in cell density. We conclude that microtubule disrupting agents are the first agents found to be effective in stimulating growth of vascular endothelium at saturation density. These data further suggest that colchicine and vinblastine stimulate cell growth in a manner similar to wounding, where cell movement is a prerequisite to cell replication.

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Release from density-dependent inhibition of growth in the absence of cell locomotion

Cited by 16 publications

References 23 publications

Thrombin potentiates the mitogenic response of cultured fibroblasts to serum and other growth promoting agents

Thrombin potentiates the mitogenic response of cultured fibroblasts to serum and other growth promoting agents

Epidermal growth factor induced membrane changes in 3T3 cells

Effects of cytoskeletal disrupting agents on replication of bovine endothelium

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