Autocrine growth stimulation of human renal Wilms' tumour G401 cells by a gastrin‐like peptide

Abstract

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.

Gastrin/cholecystokinin type B receptors in the kidney: molecular, pharmacological, functional characterization, and localization

“…Thus, gastrin might act as a growth factor in the kidney via specific CCK B R. Similar effects have been shown in the nephroblastoma cell line [16], but also in other cell lines from non-gastrointestinal origin, such as human small-cell lung cancer (SCLC)cells [45,46]. Gastrin might also have influences on the remodelling of the kidney architecture during the progression of renal disease and even be an important growth factor in patients with renal carcinoma [12].…”

“…Although very little is currently known of the function of these peptides in this organ, several investigators have described elevated serum gastrin levels in patients with chronic renal failure, suggesting an important role for the kidney in peptide hormone degradation [10]. Moreover, gastrin might have a direct effect on renal blood flow, natriuresis and renal growth [9][10][11][12]. However, little is known whether these effects are mediated by specific hormone receptors.…”

Selective CCK‐A but not CCK‐B receptor antagonists inhibit HT‐29 cell proliferation: synergism with pharmacological levels of melatonin

“…A relationship between CCK‐A and CCK‐B receptors and cancer growth exists and thus, several CCK‐A and/or CCK‐B receptor antagonists have been tested as to their antiproliferative effects on human colonic cancer cell lines. Proglumide, a nonselective CCK‐A/B receptors antagonist and lorglumide, a CCK‐A receptor antagonist, inhibit the basal growth of colonic cancer [9, 13]. Selective CCK‐B antagonists such as L 365,260, inhibit the gastrin‐induced HT‐29 cells proliferation [9], whereas L364,718, a selective CCK‐A antagonist, inhibits human pancreatic cancer growth [14].…”

Expression and processing of gastrin in pancreatic adenocarcinoma

“…It has been shown to promote the growth of both normal gastrointestinal mucosa 1 as well as gastrointestinal cancers including colon cancer 2 and stomach cancer 3 . Gastrin also has been shown to promote the growth of pancreatic carcinoma 4 , hepatocellular carcinoma 5 , renal cell carcinoma 6 and small cell carcinoma of the lung 7 .…”