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bombesin/gastrin releasing peptide
anchorage-independent growth activity
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abbr. BN, BBS, BBN. Also: BOM; also: BN/GRP.
Bombesin is one of the active peptides purified originally from amphibian skin (Anastasi et al, 1971). Bombesin is a neuropeptide found in the central and peripheral nervous system of amphibians (Bombina bombina). Bombesin-like peptides are produced by neurons of the central and peripheral nervous system, and many other neuroendocrine cell types.
Bombesin is a small peptide of 14 amino acids.
Bombesin-like peptides are grouped into three families, based upon sequence identities in the eight carboxyterminal amino acids, which are also responsible for the biological activities and receptor binding. These families are the Bombesin family, Ranatensin family, and the Phyllolitorin family. The factors known as neuromedins (see also: Tachykinins) are members of the Ranatensin subfamily. Human GRP (gastrin releasing peptide) is a member of the Bombesin subfamily, referred to as Mammalian Bombesin or BLP [Bombesin-like peptide]. GRP is considered a homolog of the amphibian bombesin.
The biological activity of bombesin is mediated by specific receptors that also bind GRP (gastrin releasing peptide) and Bombesin-like factors. Three bombesin receptor subtypes, termed gastrin releasing peptide receptor (GRPR; called also BB2 receptor), neuromedin B receptor (NMBR; called also BB1 receptor), and bombesin receptor subtype 3 (BRS-3; called also BB3 receptor), have been identified in rodents and humans. These receptors are expressed in many different cell types and tissues, including 3T3 cells, rat pituitary adenomas, pancreatic cells, gastrin-producing cells, brain.
Bombesin and Bombesin-like factors show a wide spectrum of biological activities. These include regulation of the contraction of smooth muscle cells, induction of the secretion of neuropeptides and hormones. Bombesin is one of the most powerful substances showing anorexic effects in the hypothalamus (Moody and Merali, 2004). Kobelt et al (2006) have reported that peripheral bombesin, unlike amylin, inhibits food intake induced by peripheral ghrelin and enhances activation of CRF neurons in the paraventricular nucleus of the hypothalamus.
In human mammary carcinomas GRP (gastrin releasing peptide, mammalian bombesin) induces the synthesis of ET (Endothelins) which acts on stromal cells of the mammary gland in a paracrine manner (see also: Stromal cell line). Bombesin is synthesized after electric stimulation of nerve cells and induces the release of gastrin and cholecystokinin in the intestines and the pancreas.
Apart from the classical role of neurohumoral hormone bombesin also acts as a growth factor and therefore shows activities of cytokines although it is not seen or classified as such due to its small size (see also: regulatory peptide factors).
In serum-free medium (see also: SFM) bombesin stimulates DNA synthesis and proliferation of murine fibroblasts (3T3 cells) in the absence of other growth factors. Several analogs of SP (substance P) competitively block the binding of bombesins to their receptor and all the events leading to mitogenesis. The growth of human mammary carcinoma cells is also enhanced by bombesin. The growth-promoting activities of bombesin are potentiated by insulin. The biological activity of bombesin as a mitogen is coupled to the activation of Ca(2+)-mobilizing G-proteins. In human alveolar macrophages bombesin-like factors modulate the synthesis of IL1.
Kresch et al (1999) have reported that Bombesin inhibits cell death by apoptosis in developing fetal rat lung. Salido et al (2000) have reported that bombesin inhibits apoptosis in several prostate cancer cell lines.
CLINICAL USE AND SIGNIFICANCE
It has been observed that bombesin can be used to increase the sensitivity of cisplatin-sensitive and resistant variants of human ovarian carvinoma cell lines to cisplatin.
Small cell lung cancers (SCLC) have been shown to secrete many bombesin-like peptides into the conditioned medium. It has been suggested that these peptides act in an autocrine manner and this view is supported by the inhibition of tumor cell growth following transplantation into the nude mouse (see also: Immunodeficient mice) and treatment with monoclonal antibodies directed against bombesins. Some transplanted tumors escaping this treatment and developing into progressively growing tumors may be the result of mutations making these cells independent of the growth factor (see also: Factor-dependent cell lines).
For other entries pertaining to low molecular weight substances that are not classified as cytokines or growth factors but that possess activities of cytokines see also: regulatory peptide factors.
See REFERENCES for entry Bombesin.
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