Effects Of GDNF On Schwann Cells Promote Proliferation And Migration Of Gastric Cancer Cells

Background Gastric cancer(GC)is one of the most common malignant tumors in the digestive system.Its high degree of malignancy and poor prognosis pose a serious threat to the health and life safety of Chinese residents.At present,the treatment for GC patients is still mainly surgical treatment and chemotherapy.Although targeted therapy and immunotherapy have been applied in clinic,the overall prognosis is still not satisfactory.Therefore,it is particularly important to explore new therapeutic strategies and targets for GC.Many studies have confirmed that the peripheral nerve may plays a significant role in promoting GC progression,and Schwann cells(SCs)may play a key role in this process.Methods Peripheral nerve and GC cells in GC tissue sections(n =20)are assessed by Immunohistochemistry(IHC)and HE staining,and the relationship between peripheral nerve and GC cells is observed.SCs were extracted and purified from rat sciatic nerve and SCs Conditioned medium(CM)was obtained.The changes in proliferation and migration of GC cells were observed by co-culture of SCs and GC cells and SCs-CM culture of GC cells.Bioinformatics methods were used to explore the key molecules and their specific receptors that changed significantly before and after the reprogramming phenotype of SCs,at the same time,Western blot(WB)and Immunofluorescence(IF)were used to detect the expression of the key molecules in SCs and GC tissues.Finally,the effects of recombinant human GDNF protein on GC cell proliferation and migration were observed.Results S-100β IHC and HE staining of GC tissue showed that GC cells surrounded peripheral nerve fibers and even infiltrated into the interior of peripheral nerve fibers.The proliferation ability of GC cells cultured by SCs-CM was significantly increased(P < 0.05).The migration ability of GC cells was significantly increased after co-culture with SCs and cultured by SCs-CM(P < 0.05),and the expression of SCs dedifferentiation phenotype molecule c-Jun was significantly up-regulated.Bioinformatics results showed that Glial cell derived neurotrophic factor(GDNF)was significantly upregulated in SCs with dedifferentiated phenotype.GDNF and its specific receptor GDNF family receptor alpha 1(GFRα-1)increased in SCs and GC tissues,respectively.Recombinant human GDNF protein can promote GC cell migration.Conclusion SCs can significantly promote GC cell proliferation and migration.The GDNF-GFRα-1 axis may play an important role in the regulation of SCs promote GC cell migration.GDNF and GFRα-1may become new therapeutic targets for GC.