Autocrine tumour growth regulation by somatomedin C: an in-vitro model.
A human primary haemangiosarcoma was derived from a patient with severe hypoglycaemia. Cell line established from that tumour secreted somatomedin C in serum-free culture media. Immunoreactive somatomedin from the media eluted from Sephacryl S-200 in two peaks of 160 000 and 8000 molecular weights. Similar results were obtained when medium was acidified and chromatographed on Sephadex G-50. Binding of tracer concentrations of 125I-labelled somatomedin C to human haemangiosarcoma cells was much higher than that of 125I-labelled insulin. Half-maximal displacement of 125I-labelled somatomedin C binding occurred at an unlabelled somatomedin C concentration of 0.7 nmol/l. Insulin competed with 125I-labelled somatomedin for binding to this receptor, but 150-fold more insulin was required for half-maximal displacement. Somatomedin secreted by human haemangiosarcoma cells and purified from serum-free media strongly stimulated [methyl-3H]thymidine incorporation into the DNA of these cells. Inhibition of somatomedin C secretion by cortisol resulted in the inhibition of tumour cell proliferation but stimulation of somatomedin secretion by human GH stimulated the cell proliferation rate. It appears that production of somatomedin C in human haemangiosarcoma cells plays a part in the regulation of tumour growth by an autocrine mechanism.
K
K
Pavelić
D
D
Vrbanec
S
S
Marusić
S
S
Levanat
T
T
Cabrijan
D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology; D006394:Hemangiosarcoma / Q000032:analysis / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology*; D008875:Middle Aged; D008954:Models, Biological; D013002:Somatomedins / Q000378:metabolism* / Q000494:pharmacology*
D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D006854:Hydrocortisone