Growth-promoting action of gastrin on human colonic and gastric tumour cells cultured in vitro.

The gastrointestinal hormone, gastrin, was examined for its trophic effect on the growth of colorectal and gastric tumour cells. All of the freshly disaggregated colorectal and gastric human adenocarcinomas responded to pentagastrin in 24 h cultures in vitro. Two newly established adenocarcinoma cell lines showed a response to pentagastrin at passage 2 but not at passage 6. Long-established cell lines did not respond to pentagastrin; however, upon synchronization of the human gastric cell line, MKN45, a trophic growth response with gastrin-17 was observed. This response was enhanced when the same cell line was grown as a xenograft in nude mice and then examined in vitro for gastrin dependence; this dependence was gradually reduced on further in vitro passaging. These results indicate that trophic responses to gastrin are lost during in vitro culture and may be underestimated by using long-established tumour cell lines. However, as all of the early cultures of colorectal and gastric tumours respond trophically to gastrin, perhaps gastrin-receptor blockers may be an important therapeutic modality for these patients.