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Bombesin (BBS, BB), is a 14-amino acid neurohormone polypeptide, derived initially from amphibians with a wide range of physiological effects in the brain, lungs, and GI tract. Bombesin regulates gastrointestinal hormone release and gastrointestinal motility.[1] Recently, studies have evaluated the role of bombesin in tumor growth, cellular proliferation, and inflammation.[2] Research has also discovered several peptides structurally related to bombesin.[3]  Two well-studied homologs are called neuromedin B and gastrin-releasing peptide (GRP).[1]  The gastrin-releasing peptide is biologically and immunologically equivalent to bombesin, making GRP the mammalian equivalent. In addition to gastric neurohormonal impacts on the GI tract, the BN-like peptides have also been shown to modulate satiety, thermoregulation, glucose homeostasis, and circadian rhythms.[4][5]

Researchers believe that neuropeptides influence feeding, satiety, energy homeostasis, and other parameters associated with weight control.[30] Those involved are bombesin, insulin, and orexins. These peptides exhibit diverse effects upon the hypothalamus by acting as ligands for G protein-coupled receptors within the brain. Some tumors can produce agents such as bombesin and adrenocorticotropic hormone, which can affect caloric processing.[31][32][33] The abnormal intake and utilization of calories contribute to the altered metabolism associated with cachexic states precipitated by tumorigenesis, which leads to a cyclical chain of events in which protein catabolism, glucose intolerance, and lipolysis cannot be augmented by the addition of calories. Inhalational exposures can precipitate an inflammatory reaction within the airways and alveoli, leading to activated neutrophils, and other inflammatory cells release proteases as part of the inflammatory process. Neutrophil-induced oxidative damage stimulates the release of profibrotic neuropeptide bombesin in the normal process of tissue repair. This mechanism appears to contribute to the pulmonary neuroendocrine cells' promotion of bombesin-like peptide immunoreactivity.[34] Studies have correlated bombesin-like immunoreactivity with the abnormal inflammatory response seen in bronchopulmonary dysplasia.[35][36] Researchers in a study of 132 infants at 28-weeks gestation or less found that bombesin-like peptide levels elevate in the urine prior to the development of bronchopulmonary dysplasia.[37] Infants who had elevated levels of the bombesin-like peptide in their urine 1 to 4 days after birth were ten times more likely to develop bronchopulmonary dysplasia.[37] Therefore, urine bombesin-like peptide screening might allow for early therapeutic interventions to minimize disease progression.

Studies have correlated bombesin-like immunoreactivity with the abnormal inflammatory response seen in bronchopulmonary dysplasia.[35][36] Researchers in a study of 132 infants at 28-weeks gestation or less found that bombesin-like peptide levels elevate in the urine prior to the development of bronchopulmonary dysplasia.[37] Infants who had elevated levels of the bombesin-like peptide in their urine 1 to 4 days after birth were ten times more likely to develop bronchopulmonary dysplasia.[37] Therefore, urine bombesin-like peptide screening might allow for early therapeutic interventions to minimize disease progression. Eosinophilic granuloma is a fibrotic lung disease almost always seen in adult cigarette smokers. One study showed that the number of pulmonary neuroendocrine cells with bombesin-like immunoreactivity increases in patients with eosinophilic granuloma.[20] Therefore neuroendocrine cell hyperplasia may lead to bombesin-like peptide elevation and subsequent monocyte and fibroblast recruitment, which contribute to granuloma formation; this would be in line with other studies which have shown bombesin to be chemotactic for monocytes and mitogenic for fibroblasts.[20] Inhibition of Ca ++ influx inhibits the release of neurotransmitters like bombesin, acetylcholine, norepinephrine, serotonin, somatostatin, and substance P. These neurotransmitters mediate pain perception in the spinal cord. Inhibition of release into the synaptic cleft leads to decreased postsynaptic neuronal firing and transmission of nociception.[38] Tumors of neuronal origin such as medulloblastoma, primitive neuroectodermal tumors, neuroblastoma, pineoblastoma are bombesin positive. Recently it has been suggested that bombesin-related peptides are involved in the autocrine stimulation of human small-cell lung carcinomas The growth and metastatic potential of neuroendocrine tumors. The molecular mechanisms and signaling pathways that are responsible for bombesin-like peptide-induced cell migration and invasion remain unclear.[23][39]

Tumors of neuronal origin such as medulloblastoma, primitive neuroectodermal tumors, neuroblastoma, pineoblastoma are bombesin positive. Recently it has been suggested that bombesin-related peptides are involved in the autocrine stimulation of human small-cell lung carcinomas The growth and metastatic potential of neuroendocrine tumors. The molecular mechanisms and signaling pathways that are responsible for bombesin-like peptide-induced cell migration and invasion remain unclear.[23][39] Bombesin exerts a stimulatory effect on the growth of human prostatic cancer cells in vitro.[34] Bombesin also has a role in prostatic epithelium growth; this would support other studies stating that prostatic carcinoma may have an endocrine, autocrine, or paracrine proliferation stimulus within the gland microenvironment.[40][41][42] This important fact provides an objective basis for the development of neuropeptides as therapeutic targets and may be helpful in the treatment of advanced prostatic carcinoma.[43][41]