Expression and its clinical significance of G-protein coupled receptor 49 in pancreatic carcinoma / 中华消化杂志

ABSTRACT

Objective To investigate the clinical significance and biological role of G-protein coupled receptor 49(GPR49) expression in pancreatic carcinoma.Methods GPR49 expression in tumor and adjacent normal tissues of 77 patients with pancreatic cancer was compared by tissue microarray and immunohistochemistry.And then, the GPR49 expression levels in the tumor tissues of patients with different pathological grades and clinical stages were analyzed.GPR49 positive pancreatic cancer cell line CFPAC-1 was taken as cellular model.CFPAC-1 cells were stimulated with roof plate-specific spondin(RSPO)1, the ligand of GPR49, in vitro.The effect of RSPO1 on CFPAC-1 cells proliferation was evaluated with cell counting.The effect of RSPO1 on the expression of membrane molecular CD44 in CFPAC-1 cells was detected by flow cytometry.CFPAC-1 cells incubated with RSPO1 were subcutaneously implanted into nude mice.And then, the time of tumor formation and tumor size were observed.T test and single factor analysis of variance were performed for statistical analysis.Results GPR49 was widely expressed in all 77 pancreatic cancer tissues.By immunohistochemistry, the score of GPR49 expression in pancreatic cancer tissues was 9.0±2.4, which was higher than that of adjacent normal tissues (5.7±2.4), and the difference was statistically significant (t=8.995, P0.05).The results of experiments in vitro indicated that RSPO1 could promote CFPAC-1 cells proliferation and up-regulate CD44 expression in CFPAC-1 cells.Experiments in vivo demonstrated that after 30 days the tumor volume of mice implanted with RSPO1-pretreated CFPAC-1 cells was (606.0±188.0) mm3, which was larger than that of PBS-pretreated group ((364.2±83.7) mm3), and the difference was statistically significant (t=2.616, P=0.031).Conclusion GPR49 is widely expressed in pancreatic cancer cells and RSPO1/GPR49 pathway has play a role in promoting the proliferation of pancreatic cancer cells, which might be a potential target for interfering pancreatic cancer.