The neuropeptide bombesin modifies the proliferative and invasive properties of tumor cells

The amphibian tetradecapeptide bombesin and its mammalian counterpart, the gastrin-releasing peptide (GRP), are neurotransmitters and paracrine hormon es. GRP is expressed mainly in nerve fibers throughout the mammalian gut an d in the central nervous system. A variety of native human tumors express t he bombesin/GRP receptor, suggesting that the peptide may also play a signi ficant role in vivo in carcinogenesis. Several recent studies have demonstr ated that GRP and bombesin could stimulate cell proliferation, migration an d invasion, and induce morphological changes associated with cytoskeleton r eorganization in cell lines of different origin. All these effects are part of the metastatic process leading to the dissemination of tumor cells. Int erestingly, the interaction of bombesin with its receptor activates several intracellular pathways in cell lines, including proliferation pathways (pr otein kinase C, MAP kinases), kinases located at the cell membrane and invo lved in migration and adhesion (p125(FAK)), and the small G proteins (Rho, Rac, Cdc42) which control the cell morphology and the actin cytoskeleton. B y understanding the intracellular pathways responsible for the pro-invasive effects of bombesin on tumor cells in vitro, it may be possible to identif y new mechanisms leading to tun;or cell dissemination, and by extension new targets for anti-tumoral therapy.