Somatomedin-C substitutes for insulin for the growth of mammary epithelial cells from normal virgin mice in serum-free collagen gel cell culture.
We investigated the effect of somatomedin C (SM-C) on the growth of mouse mammary ductal epithelial cells in collagen gel culture. Epithelial cells, isolated by collagenase digestion of whole glands, were placed into primary serum-free collagen gel cell culture for 10-12 days, during which SM-C was added alone or in combination with other growth-promoting factors. Previous work has shown that these cells require a superphysiological concentration of insulin (10 micrograms/ml) for optimum growth in serum-free medium (a 1:1 mixture of Ham's F-12 and Dulbecco's Modified Eagle's medium) containing epidermal growth factor (EGF). When SM-C (1-250 ng/ml) alone was added to serum-free basal medium containing EGF, it stimulated growth (at concentrations greater than 25 ng/ml) to at least the same extent as insulin at 10 micrograms/ml. There was no additive stimulation of growth when optimal concentrations of insulin and SM-C were added together. The nonadditive stimulation at optimal concentrations of these hormones may indicate that the previous requirement for a superphysiological concentration of insulin for maximum growth was due to low affinity binding of insulin to the SM-C receptor. Rat insulin-like growth factor II (Collaborative Research) at 50-200 ng/ml did not stimulate growth in the presence or absence of insulin. SM-C could not stimulate growth alone. The presence of EGF or mammogenic hormones (progesterone and PRL) was required.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells; D005260:Female; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008321:Mammary Glands, Animal / Q000166:cytology*; D051379:Mice; D011374:Progesterone / Q000494:pharmacology; D011388:Prolactin / Q000494:pharmacology; D013002:Somatomedins / Q000494:pharmacology*
D007328:Insulin; D013002:Somatomedins; D011374:Progesterone; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D011388:Prolactin; D003094:Collagen