Ghrelin's modulation of growth hormone secretagogue receptors in primary glioblastoma and meningioma: A comprehensive in-vitro study

Growth hormone secretagogue receptors (GHSR), which bind peptide hormone ghrelin, are found in numerous malignancies and healthy tissues including the brain. The objective of this study was to investigate if ghrelin has a proliferative or anti-proliferative effect on primary cell lines isolated from brain tumors. Methods: Following craniotomy, tumor tissue samples were promptly collected, tumor cell lines were generated, and a range of concentration-dependent effects of ghrelin were assessed using immunofluorescence, flow cytometry, growth assays, and scratch assays. The expression of the Ki-67 protein was assessed using a Ki-67 monoclonal antibody, while the GHSR1 antibody was employed to quantify the GHSR in tumor cells. Results: An increase in cell proliferation was observed at 20 nano Molar (nM) ghrelin concentration, while a concentration surpassing 20 nM exhibited antiproliferative effects. Tumor cell migration and proliferation were enhanced when ghrelin at a concentration of 20 nM was applied to a 6-well plate; induced gaps were filled within three days following the scratch assay. Immunofluorescence assay revealed that cells treated with 20 nM ghrelin had high Ki-67 expression, low GHSR expression, and decreased apoptosis compared to control cells. Conversely, cells treated with 50 nM ghrelin had higher levels of GHSR expression and decreased Ki-67 expression, while overall increased apoptosis. Conclusions: We conclude that ghrelin exhibited a proliferative effect on tumor cells in low concentrations (up to 20 nM), whereas a higher concentration of 50 nM and above showed an anti-proliferative effect. Therefore, we suggest that, for therapeutic purposes, caution should be taken while deciding the dose of ghrelin.