Synergistic effects of epidermal growth factor and thrombin on the growth stimulation of diploid Chinese hamster fibroblasts.
The serum supplement used in the culture of a variety of mammalian cells can be replaced by known growth factors. Diploid Chinese hamster fibroblasts (CHEF/18) will grow for several days in a medium (4F) supplemented with four growth factors: epidermal growth factor (EGF), insulin, fibroblast growth factor (FGF), and transferrin. The growth rate is only about 50% as fast as when fetal calf serum is added. This difference is eliminated by thrombin (10--100 ng/ml; 0.3--3 nM). The CHEF/18 cell line is unique in that no other cell line responds to thrombin in this concentration range. Thrombin acts synergistically with other growth factors to stimulate CHEF/18 cell growth. By itself, thrombin is only mitogenic at elevated concentrations. Thrombin can largely compensate for the absence of EGF and partly for the absence of insulin in serum-free media. Chemically and "spontaneously" transformed cell lines related to CHEF/18 have lost requirements for both EGF and thrombin, and have retained requirements for insulin and transferrin expressed by CHEF/18. No CHEF cells in this work required FGF. These results suggest that the mechanisms by which EGF and thrombin stimulate cells to grow are related.
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D006224:Cricetinae; D004247:DNA / Q000096:biosynthesis; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005347:Fibroblasts; D007328:Insulin / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology*; D014168:Transferrin / Q000494:pharmacology
D007328:Insulin; D010455:Peptides; D014168:Transferrin; D004815:Epidermal Growth Factor; D004247:DNA; D013917:Thrombin