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Annexin A2and Annexin A2Receptor Promote Angiogenesis Of Pancreatic Cancer

Posted on:2015-08-11Degree:MasterType:Thesis
Country:ChinaCandidate:H D JiangFull Text:PDF
GTID:2284330467459234Subject:Genetics
Abstract/Summary:PDF Full Text Request
Pancreatic cancer is one of the global high incidence of tumor, and embraces extremelyhigh metastatic, mortality. The pancreas is a retroperitoneal organ, lack of effective clinicaldiagnosis biomarker, lead to the early diagnosis rate is low, poor prognosis,5years ofsurvival rate <6%. Therefore investigating whether the molecule associated with pancreaticcancer metastasis and clinical diagnostic significance is urgent needed. Membrane couplingprotein A2(Annexin A2, ANXA2) are expressed in human tissues, especially inproliferation of cells express is higher. A large number of experimental evidence shows thatthe higher protein expression in most tumor cells, closely related with tumor invasion andmetastasis. Membrane receptors associated protein A2(Annexin A2Receptor, AX2R) isalso associated with the adhesion, invasion and metastasis of tumor cells, but its study aboutthe angiogenesis of tumor is still blank. Therefore, this topic mainly explore the ANXA2and its receptor play the role in the angiogenesis process of pancreatic cancer.We chose107patients with pancreatic cancer,19cases of patients with acute pancreatitis(AP),30cases of chronic pancreatitis (CP) patients with serum specimens, using enzyme-linked immunosorbent (ELISA) method, the ANXA2content in serum were detected; ReuseqRT PCR and immunohistochemical experiment results from the level of gene and proteinin the cancer tissue ANXA2expression level. Combined with the clinical pathological datafor statistical analysis of experimental results discussed ANXA2in the clinical anddiagnostic value of pancreatic cancer.After the success of down regulation ANXA2expression in pancreatic cancer cell lines and AX2R expression in vascular endothelial cellline, as the research object, by ELISA and Western Blot, immunofluorescence localization,cell proliferation (CCK-8), and other experimental technology, discussed ANXA2oncytology effects on angiogenesis. Compared to the experimental results demonstrated thatpatients with acute pancreatitis, the amount of ANXA2expression in pancreatic cancerpatients serum is higher, separately USES the diagnosis of pancreatic cancer than CA199inthe diagnosis of sensitivity and speciality degree were improved. And ANXA2expressionin the cancer tissue than tissue adjacent to carcinoma. Cytology results also confirmed that can secrete ANXA2pancreatic cancer cell lines, the proteins can be combined with vascularendothelial cell membrane surface AX2R mutually, by activation of MAPK related protein(AKT, ERK1/2), in turn, promotes endothelial cell proliferation, and that is one of the keylink in the process of angiogenesis. Finally, to verify the cytology results, we established theanimal model of pancreatic transplanted tumor, immunohistochemistry andimmunofluorescence test results also confirmed ANXA2expression silence can inhibittumor angiogenesis.Therefore, the above clinical, cells, and the results of animal experiments, we draw theconclusion: in patients with pancreatic cancer tissue and serum ANXA2expression level ishigher, the high level of ANXA2mainly comes from the tumor cells, it can promote vascularendothelial cell proliferation, in turn, promote angiogenesis induced by tumor, this suggeststhat ANXA2not only can be used as a clinical differentiation potential markers for diagnosisof pancreatic cancer, can also be used as a potential therapeutic targets of inhibitingangiogenesis of pancreatic cancer.
Keywords/Search Tags:Annexin A2, Annexin A2receptor, pancreatic cancer, angiogenesis, CD31
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