The effect of Wnt5a derived from tumor associated fibroblasts on the invasion and migration of gastric cancer cells and its correlation with clinicopathological features of gastric cancer
Objective To investigate the effect of Wnt5a derived from tumor-associated fibroblasts(CAFs)on the migration and invasion of gastric cancer cells.Methods The differentially expressed genes Wnt5a between CAFs and normal gastric fibroblasts(NGFs)in gastric cancer tissues and their corresponding normal gastric tissues using the GEO database GSE194261 dataset were screened.Immunohistochemical method was used to detect the expression of Wnt5a protein in tissue samples of clinical gastric cancer patients,and the relationship between Wnt5a protein expression and clinicopathological features of gastric cancer was analyzed.CAFs and NGFs were extracted from fresh surgical specimens of gastric cancer patients,and the expression of Wnt5a in CAFs was detected by real-time fluorescence quantitative-polymerase chain reaction and Western blot experiment.Transwell invasion and migration experiment was used to observe the effects of CAFs,inhibition of Wnt5a expression in CAFs and different concentrations of recombinant Wnt5a protein on the migration and invasion ability of gastric cancer MGC-803 and MKN-28 cell lines in vitro.Results Through the screening of GEO database GSE194261 data set,it was found that Wnt5a was more expressed in CAFs than NGFs(P＜0.05).Immunohistochemical results showed that the expression of Wnt5a protein in gastric cancer tissues was significantly stronger than that in normal gastric tissues(P＜0.05),and the expression of Wnt5a protein was related to T stage of tumor(x2=5.035,P＜0.05),but not related to gender,age,degree of tumor differentiation,lymph node metastasis,vascular invasion and nerve invasion(P＞0.05).Inhibiting Wnt5a derived from CAFs could inhibit the invasion and migration of gastric cancer cells.By stimulating gastric cancer cells with different concentrations of human recombinant Wnt5a protein,it was found that when the concentration of human recombinant Wnt5a protein was greater than 100 ng/mL,the invasion and migration abilities of MGC-803 and MKN-28 gastric cancer cells were significantly increased(P＜0.05).Conclusion Wnt5a is highly expressed in CAFs derived from the interstitial tissue of gastric cancer,which is related to the invasion depth of gastric cancer and can promote the invasion and migration of gastric cancer cells.
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