Abstract
Two colorectal (HT29, LoVo) and one gastric (MKN45) human tumour cell lines were examined for their in vitro trophic response to human gastrin-17. MKN45 and HT29 responded by increased 75Se selenomethionine uptake to exogenous gastrin (139 +/- 5.5% and 123 +/- 3% of control values respectively) whereas LoVo showed no significant response to this hormone. When these same cell lines were grown as xenografts in nude mice, similar responses were seen to exogenously administered human gastrin-17 (10 micrograms mouse-1 day-1, subcutaneous injection). MKN45 xenografts showed a greater response to continuously administered gastrin (osmotic mini-pumps, (10 micrograms mouse-1 day-1) when compared to the same dose given via a subcutaneous bolus injection. The hormone-treated xenografts had a two-fold increase in tumour cross-sectional area and growth rate when compared to saline-treated controls. Dose-response studies revealed that 0.4 micrograms gastrin mouse-1 day-1 appeared to be the minimally effective dose. As gastric and colorectal tumour cells show a trophic response to gastrin, antagonists of the gastrin receptor may prevent this effect causing tumour stasis. The gastric tumour cell line, MKN45, is gastrin-responsive and would be an ideal model for screening potent receptor antagonists.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Borch K., Renvall H., Liedberg G., Andersen B. N. Relations between circulating gastrin and endocrine cell proliferation in the atrophic gastric fundic mucosa. Scand J Gastroenterol. 1986 Apr;21(3):357–363. doi: 10.3109/00365528609003087. [DOI] [PubMed] [Google Scholar]
- Carter A. C., Sedransk N., Kelley R. M., Ansfield F. J., Ravdin R. G., Talley R. W., Potter N. R. Diethylstilbestrol: recommended dosages for different categories of breast cancer patients. Report of the Cooperative Breast Cancer Group. JAMA. 1977 May 9;237(19):2079–2078. [PubMed] [Google Scholar]
- Johnson L. R. New aspects of the trophic action of gastrointestinal hormones. Gastroenterology. 1977 Apr;72(4 PT2):788–792. [PubMed] [Google Scholar]
- Lichtenberger L., Miller L. R., Erwin D. N., Johnson L. R. Effect of pentagastrin on adult rat duodenal cells in culture. Gastroenterology. 1973 Aug;65(2):242–251. [PubMed] [Google Scholar]
- McGregor D. B., Jones R. D., Karlin D. A., Romsdahl M. M. Trophic effects of gastrin on colorectal neoplasms in the rat. Ann Surg. 1982 Feb;195(2):219–223. doi: 10.1097/00000658-198202000-00017. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McGuigan J. E., Trudeau W. L. Serum and tissue gastrin concentrations in patients with carcinoma of the stomach. Gastroenterology. 1973 Jan;64(1):22–25. [PubMed] [Google Scholar]
- Miller L. R., Jacobson E. D., Johnson L. R. Effect of pentagastrin on gastric mucosal cells grown in tissue culture. Gastroenterology. 1973 Feb;64(2):254–267. [PubMed] [Google Scholar]
- Sirinek K. R., Levine B. A., Moyer M. P. Pentagastrin stimulates in vitro growth of normal and malignant human colon epithelial cells. Am J Surg. 1985 Jan;149(1):35–39. doi: 10.1016/s0002-9610(85)80006-4. [DOI] [PubMed] [Google Scholar]
- Sumiyoshi H., Yasui W., Ochiai A., Tahara E. Effects of gastrin on tumor growth and cyclic nucleotide metabolism in xenotransplantable human gastric and colonic carcinomas in nude mice. Cancer Res. 1984 Oct;44(10):4276–4280. [PubMed] [Google Scholar]
- Walsh J. H., Grossman M. I. Gastrin (first of two parts). N Engl J Med. 1975 Jun 19;292(25):1324–1334. doi: 10.1056/NEJM197506192922505. [DOI] [PubMed] [Google Scholar]
- Watson S. A., Durrant L. G., Morris D. L. Growth-promoting action of gastrin on human colonic and gastric tumour cells cultured in vitro. Br J Surg. 1988 Apr;75(4):342–345. doi: 10.1002/bjs.1800750416. [DOI] [PubMed] [Google Scholar]
- Winsett O. E., Townsend C. M., Jr, Glass E. J., Thompson J. C. Gastrin stimulates growth of colon cancer. Surgery. 1986 Mar;99(3):302–307. [PubMed] [Google Scholar]