The Role Of CD97 Isoforms In Gastric Carcinoma

Background:The aim of this study was to elucidate the role of CD97 isoforms in gastric carcinoma.Methods:Out of four gastric cancer cell lines investigated, BGC-823 cells demonstrating low CD97 protein expression were stably transfected with pcDNA3.1 vector containing CD97/EGF1,2,5 or CD97/EGF1-5 inserts. SGC-7901 and MGC-801 cells demonstrating high CD97 expression were transfected with pGCsilencer-CD97/EGF 1,2,5 RNAi and pGCsilencer-CD97/EGF1-5 RNAi plasmids. Behavior of transfected cells was systematically investigated by employing proliferation, motility and invasive assays. Possible signal pathways were also searched in this experiment.Results:We found that:①The invasive ability of different gastric cancer cell lines were not positively correlated with total CD97 protein expression but with the expression of CD97 small isoforms;②Over-expression of CD97/EGF1,2,5 isoform correlated with increased motile and invasive ability of the clones, while CD97/EGF1-5 clones revealed significantly reduced invasive properties as compared with corresponding controls;③Decreased and invasive ability was found in pGCsilencer-CD97/EGF1,2,5 RNAi clones, which had increased cell motile and migration. The cell motile, invasive and migrative ability were all decreased in pGCsilencer-CD97/EGF1-5 RNAi clones;④Cdc42 an stathmin levels were elevated in BGC-CD97/EGF1-5 clones but down-regulated in BGC-CD97/EGF1,2,5 clones;⑤The levels of Rac,LIMK1 and phosphorylated-cofilin were significantly elevated in BGC-CD97/EGF1,2,5 clones as compared to the control;⑥Ratio of a-tubulin/acetylated-tubulin were higher in BGC-CD97/EGF1,2,5 clones than in BGC-CD97/EGF1-5 clones.Conclusion:CD97 is closely related with advanced stages and higher invasiveness of gastric carcinoma. This study confirmed that the total CD97 protein expression is not positively correlated with the invasiveness of gastric cancer cells. Furthermore, the study lightened the tumor promoting role of CD97 small isoform in cancer progression and indicated the Cdc42-Stathmin-tubulin and Rac-LIMK1-cofilin pathway as well as the changes in acetylation status were prompted as possible mechanisms affecting invasive behavior of transfected cells.