Autocrine growth stimulation of human renal Wilms' tumour G401 cells by a gastrin-like peptide.
The role of gastrin in the control of growth of renal G401 cells isolated from a human nephroblastoma (Wilms' tumour) was investigated. G401 cell growth was enhanced in the presence of exogenous gastrin. Addition of anti-gastrin antibodies to serum-free medium significantly inhibited the growth of G401 cells. G401 cells contained the equivalent of 4.3 pg/10(6) cells of gastrin, and serum-free medium collected over 48 hr from G401 cells contained the equivalent of 38 ng/10(6) cells of gastrin, as determined by radioimmunoassay. Growth of G401 cells was inhibited in a concentration-related way by a variety of gastrin/CCK receptor antagonists. Devazepide and proglumide were, respectively, the most and the least potent inhibitors of G401 cell growth (potency order devazepide > L-365,260 = lorglumide > loxiglumide > benzotript > proglumide). These gastrin/CCK receptor antagonists had similar growth-inhibitory activities in human colonic adenocarcinoma HCT-116 cells. Growth of HCT-116 cells was stimulated to a lesser extent, as compared with G401 cells, by exogenous gastrin, and endogenous gastrin was not detectable in HCT-116 cells. The results are consistent with a role for a gastrin-like peptide in the control of growth of a renal cell line. The data suggest that gastrin/CCK receptor antagonists warrant further investigation as therapeutic agents for the control of gastrin-responsive tumours derived from outside, as well as inside, the gastrointestinal tract, including tumours derived from the kidney.
Blackmore
M
M
Department of Physiological Sciences, University of Newcastle upon Tyne, Medical School, UK.
Doherty
E
E
Manning
J E
JE
Hirst
B H
BH
D001549:Benzamides / Q000494:pharmacology; D001570:Benzodiazepinones / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D020109:Devazepide; D005755:Gastrins / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000473:pathology*; D008536:Meglumine / Q000031:analogs & derivatives / Q000494:pharmacology; D010671:Phenylurea Compounds; D011377:Proglumide / Q000031:analogs & derivatives / Q000494:pharmacology; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured; D009396:Wilms Tumor / Q000473:pathology*
D001549:Benzamides; D001570:Benzodiazepinones; D005755:Gastrins; D007211:Indoles; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C065600:PD 135158; C065599:PD 134308; C058121:L 365260; D008536:Meglumine; C053737:loxiglumide; D011377:Proglumide; D020109:Devazepide; C048181:lorglumide; C013841:benzotript