Hyperexpression Of Galectin-1 In Pancreatic Stellate Cells Induces Angiogenesis And Promotes The Development Of Pancreatic Cancer

Background and objective:Pancreatic cancer is a digestive tract malignant tumor with low resection rate and poor prognosis.Its morbidity and mortality are almost the same.Smoking,obesity,alcoholism,chronic pancreatitis,diabetes mellitus,exposure to aniline and benzene compounds are risk factors.About 5%-10%of pancreatic cancer patients have genetic background.The high mortality rate of pancreatic cancer has long been a major problem for clinical surgeons.In recent years,with the continuous efforts of many scholars,considerable progress has been made in the study of pancreatic cancer.For resectable pancreatic cancer patients,adjuvant chemotherapy after operation has become the standard treatment.Molecular targeted drugs Erlotinib and GemErlo have been proved effective in the pre-treatment study of advanced unresectable pancreatic cancer,but the effect is limited.Regrettably,according to the latest research published by the American Society of Clinical Oncology(ASCO),Gem Erlo treatment does not improve the patient’s disease-free survival and overall survival.In terms of basic research,great achievements have been made in genomics,metabonomics and cancer microenvironment.At present,with the progress of science and technology and the continuous development of research,people gradually realize that the concept of only focusing on cancer cells in the past can not help people fully understand cancer,and gradually realize that the role of tumor microenvironment in the occurrence and development of cancer is becoming increasingly prominent[4,5].Many studies have further shown that pancreatic stellate cells(PSCs)in pancreatic cancer microenvironment are closely related to the occurrence and development of pancreatic cancer[2-4],and play an important role in angiogenesis,immune escape,invasion and metastasis of pancreatic cancer[5-10].It is well known that angiogenesis is an important step in the invasion and metastasis of solid tumors.However,the relationship between microenvironment and angiogenesis of pancreatic cancer is relatively rare.Recent studies have shown that galectin-1 is closely related to angiogenesis[14-16].To this end,we studied the relationship between galactose Galectin-1 secreted by PSCs in pancreatic cancer microenvironment and angiogenesis and development of pancreatic cancer and its mechanism.Method:1)The expression of Galectin-1 and platelet-endothelial cell adhesion molecule(PECAM-1,CD31)and vascular endothelial growth factor(VEGF)in 66 pancreatic cancer patients from March 2011 to May 2015 were detected by immunohistochemical method.2)PSCs were co-cultured with pancreatic cancer cells and human umbilical vein endothelial cells(HUVECs),respectively,in Galectin-1 interference group,control group and over-expression group,and then transwell,tubuloplasty and Western Blot were performed.3)The tumorigenicity of PSCs(including Galectin-1 interference group,control group and overexpression group)co-cultured with pancreatic cancer cells was studied in vivo,and the expression of Galectin-1 and CD31 was observed by immunohistochemical staining.Result:1).The expression of Galectin-1 in pancreatic cancer was positively correlated with the expression of vascular endothelial growth factor,CD31 and CD31(R2=0.463,P<0.001,with statistical significance,R2=0.270,P<0.001,with statistical significance).2).The migration and angioplasty ability of HUVECs co-cultured with Galectin-1 overexpressed PSCs were significantly higher than those of the control group,while the interference group was significantly weakened(P<0.05,the difference was statistically significant).3).After co-culture of pancreatic cancer cells with PSCs overexpressed by Galectin-1,the target protein was detected by WB assay.The results showed that the expression level of vascular endothelial growth factor receptor 2(Vascular Endothelial Growth Factor Receptor 2)was significantly higher than that of the control group,and the phosphorylation level of vascular endothelial growth factor receptor 2(Vascular Endothelial Growth Factor Receptor 2),while the interference group was significantly weakened(P<0.05,the difference was statistically significant).4).Animal tumorigenesis experiment showed that the expression of CD31 in Galectin-1 overexpression group was significantly higher than that in control group,while the expression of Galectin-l in interference group was significantly lower(p<0.05,the difference was statistically significant),and the expression of Galectin-1 was positively correlated with the expression of CD31(R2=0.730,P<0.001,the difference was statistically significant).Conclusion:1).Overexpression of Galectin-1 in PSCs in pancreatic cancer microenvironment is closely related to angiogenesis in pancreatic cancer tissues.2.Overexpression of Galectin-1 by PSCs in pancreatic cancer microenvironment induces phosphorylation of VEGFR2,which promotes angiogenesis in pancreatic cancer tissues and thus promotes the occurrence and development of pancreatic cancer.