438회 L1 cell adhesion molecule contributes to chemoresistance in intra…

438회 

연사:  홍 효 정, 강원대학교 의생명과학대학 분자생명과학부 시스템면역과학전공

제목: L1 cell adhesion molecule contributes to chemoresistance in intrahepatic cholangiocarcinoma cells

Abstract 

Cholangiocarcinomas (CC) are malignant tumors that arise from the bile duct epithelium. CC is the second most common primary hepatic malignancy and occurs at a higher incidence in Southeast Asia than in Europe and North America, but the incidence and mortality rates are increasing worldwide. The tumor is refractory to conventional chemotherapy and radiation treatment. Thus, survival among patients with unresectable CC is generally less than 12 months after diagnosis. To improve the survival of patients with CC, combinations of chemotherapeutic agents such as gemcitabine, platinum-based agents, and 5-fluorouracil have been tested, but the median survival remains low. The failure of chemotherapy is largely based on the escape of tumor cells from drug-induced apoptosis by acquired resistance to chemotherapeutic drugs. Therefore, investigation of molecular mechanisms underlying chemoresistance of CC is urgently needed to improve drug response and patient survival in the treatment of CC. Recently, we identified by immunohistochemistry that L1CAM is aberrantly expressed in 40.5% of intrahepatic CC tumors and in 42.7% of extrahepatic CC tumors. In addition, we found that high expression of L1CAM is an independent poor prognostic factor predicting overall survival in patients with ECC and that L1CAM plays a crucial role in tumor progression of ICC by promoting proliferation, migration, invasion, and survival of ICC tumor. In this study, in an attempt to examine whether the ICC tumor cells acquire resistance to apoptosis induced by chemotherapeutic drug, the cells were exposed to cisplatin for six months. Finally, we generated cisplatin-resistant (SCK^R) cells which acquired resistance to 5-fluorouracil (5-FU) and gemcitabine as well. The molecular mechanisms underlying chemoresistance in SCK^R cells will be presented.