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01-Jun-2009
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Arch Hellen Med, 26(2), March-April 2009, 195-205 REVIEW The role of ghrelin in gastrointestinal tract cancer D. NIKOLOPOULOS, G. KOURAKLIS |
Ghrelin is a recently identified 28 amino acid peptide, with pituitary growth hormone (GH) releasing activities in humans and other mammals. It is secreted mainly by the stomach mucosa into the systematic circulation. It is also expressed widely –in high or low concentrations– in different tissues, in physiological and neoplastic conditions, supporting the theory that ghrelin exerts variable endocrine, exocrine and paracrine effects in normal tissues –regulating feeding behavior, glucose and insulin blood levels, motility and secretion of the gastrointestinal tract, exerting cardiovascular effects and immunological effects, and regulating cell proliferation efficiency– as an autocrine and/or paracrine function in neoplasia. Ghrelin has been identified both at mRNA and protein levels in several endocrine and non-endocrine cancer tumors in vivo, as well as in their related neoplastic cell lines in vitro (pituitary adenomas; gastro-entero-pancreatic and pulmonary carcinoids; colorectal neoplasms; thyroid tumors; lung, breast, and pancreatic carcinomas). The pleiotropic actions of ghrelin are mediated via its receptor, known as GH secretagogue receptor (GHS-R), subtypes 1a and 1b. This review summarizes data available on (a) the structure of the ghrelin molecule and its receptor, (b) its tissue contribution in physiological and neoplastic conditions, and (c) ghrelin’s possible role in carcinogenesis and specifically in gastrointestinal tract cancer. Ghrelin and its receptor comprise a possible and promising target for the elaboration of new drugs for gastrointestinal tract cancer.
Key words: Gastrointestinal tract cancer, Ghrelin, Ghrelin receptor or receptor of GHSs (GHS-R), Growth hormone secretagogues (GHSs).