fapα在胰腺癌细胞中表达及其对胰腺癌生物学行为影响word格式论文.docx

第二军医大学博士学位论文 FAP-α 在胰腺癌细胞中的表达及其对胰腺癌生物学行为的影响 -  PAGE 8 - -  PAGE 9 - Expression of FAP-α in pancreatic cancer cells and its effect on biological behaviour of pancreatic cancer Abstract Background and objective Pancreatic cancer remains to be a highly lethal disease, with the overall 5-year survival rate being less than 5% and with the ratio of morbidity to mortality being 1:0.99. Only 20% of the patients are able to receive surgery treatment at the diagnosis, and 80% of the patients have unresectable lesions when they were diagnosed. Pancreatic ductal adenocarcinoma (PDAC) is the most frequently seen pancreatic cancer, accounting for 85%-90% of the total pancreatic cancer cases. A hallmark of PDAC is its extensive desmoplastic reaction; it has been shown that among all epithelial cancers PDAC has the most severe desmoplastic reaction, which is believe to contribute to the development, progression, metastasis, prognosis, and drug-resistance of cancer. Moreover, desmoplastic reaction is closely related with the tumor-associated fibroblasts (TAFs) in tumor stroma. TAFs can exert its effect on tumor stroma by expressing various proteins and other ways. Fibroblast activation protein -α(FAP-α) is a characteristic protein expressed by TAFs. In recent years, targeted therapy of tumors have been a focus of tumor research, and these targeted therapy aim at the molecules associated with the tumors, and to search for ideal target molecules is the key to the therapy. And TAFs is believed to be one of the most potential targets. Fibroblast Activation Protein-α(FAP-α) is an integral membrane serine peptidase originally identified as an inducible antigen expressed on TAFs, and it appears to act as a proteolytically active 170-kDa dimmer, capable of degrading many dipeptides and type I collagen. And these activities of FAP-αcan be seen in primary epithelial tumors, and it is deemed to play important roles in the formation, remodeling and maintenance of tumor stroma. Study has s