A role of ghrelin in canine mammary carcinoma cells proliferation, apoptosis and migration

The highest expression of ghrelin was observed in metastatic cancers whereas the lowest expression of ghrelin receptor was detected in tumors of the 3rd grade of malignancy. Higher expression of ghrelin and its receptor was detected in cancer cell lines isolated from metastases than in cell lines isolated from primary tumors. In vitro experiments demonstrated that exposure to low doses of ghrelin stimulates cellular proliferation, inhibits apoptosis and promotes motility and invasion of canine mammary cancer cells. Growth hormone secretagogue receptor inhibitor ([D-Lys3]-GHRP6) as well as RNA interference enhances early apoptosis.The presence of ghrelin and GHS-R in all of the examined canine mammary tumors may indicate their biological role in cancer growth and development. Our experiments conducted in vitro confirmed that ghrelin promotes cancer development and metastasis.Ghrelin was identified in human and rat stomach in 1999 by Kojima et al. [1] as endogenous ligand for growth hormone secretagogue receptor type 1a (GHS-R1a). It belongs to the G protein coupled receptor family and is widely distributed along various tissues. GHS-R has two variants of splicing: functional type 1a and truncated type 1b, which arises from an alternative splicing and its function is still unclear [2,3].The GHS-R activation in pituitary results in considerably increased secretion of growth hormone (GH). This is the main effect of ghrelin activity in humans and in animals. Ghrelin is a highly conserved peptide among various species [1,4]. It is mainly produced by endocrine X/A-like cells of stomach’s submucosal layer and, secreted directly into the blood [5]. However, the presence of ghrelin has also been detected in other areas of gastrointestinal tract, as well as in many other tissues [6].In healthy dogs, ghrelin regulates feeding behavior and energy metabolism. Plasma ghrelin levels increase before feeding time, and decrease after eating. These changes are associated with the insul