Bombesin, calcium homeostasis and tumour growth

Abstract

Bombesin and its analogues are a family of naturally occurring neuropeptides with potent mitogenic activity. The ability of this agent to induce Ca2+ transients is likely to be relevant in this context, but it is not yet clear whether the effect of bombesin on cell growth is directly and exclusively related to its capacity to increase cytoplasmic Ca2+ levels. The present study investigates the affect of bombesin on cytoplasmic Ca2+ concentrations in human tumour cells of different origin: lung adenocarcinoma, lung adenocarcinoma with properties of alveolar epithelial cells (A549 cell line), mesothelioma and uterine carcinoma (HeLa cell line). Furthermore, the ability of bombesin to promote the in vitro growth of the same cells has been analysed. This agent was able to induce a transient rise in cytoplasmic Ca2+ levels in tumour cells from all lines. In lung adenocarcinoma cells, but not in the other tumour cells, bombesin produced Ca2+ transients followed by a moderate but sustained elevation of Ca2+ levels. The effects of bombesin on tumour cell cytoplasmic Ca2+ levels were compared to those of other agents, i.e. adenosine diphosphate (ADP), collagen or thrombin, which have been reported to induce Ca2+ transients in tumour cells. Bombesin and ADP increased cytoplasmic Ca2+ levels in all cell lines, while collagen and thrombin gave rise to higher transients, but were effective only in some tumour cells and not in others. Furthermore, bombesin was able to stimulate in vitro growth of all the tumour cells, except for the A549 cells, in which this agent induced a slightly lower increase in cytoplasmic Ca2+ concentration. These data may aid a better understanding of the complex relationship between the Ca2+ mobilizing and mitogenic activities of bombesin and may be of general interest when considering the biological effects of growth-stimulating factors.