2013-10-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/642691摘要：外質體(exosome)為胞器膜所形成的小型囊泡， 藉由輸送其內含的成分(如細胞素)，外質體可改變微環境形成有利腫瘤轉移的溫床。吾人假設，胃癌會藉由外質體輸送免疫抑制分子或致癌蛋白到淋巴系統，以促進胃癌的淋巴轉移。 首先，吾人計畫收集不同期別胃癌病患的(A)原發胃癌組織、(B)引流腫瘤之淋巴結、及(C)血清的外質體，分析這三者所含免疫抑制分子(IL-6、TNF、PD-L1 等) ，蛋白酶(MMP)及致癌蛋白(c-Met)，再參照胃癌期別， 研究外質體做為胃癌改變淋巴結微環境以利轉移的相關，並以外質體做為胃癌預後指標的參考性。再者，以胃癌細胞株實驗，分析外質體和 naïve T 細胞共同培養後 regulatory T 細胞比例是否增加，以證明胃癌分泌的外質體會抑制免疫功能，以利腫瘤轉移。最後，再以動物實驗分析，注射胃癌外質體的小鼠，其影響腹腔內胃腫瘤轉移和微環境改變的情形。 本研究預期能以外質體建立新的胃癌預後指標，並針對外質體發展新 療法，以減抑胃癌的淋巴轉移。<br> Abstract: Exosomes are small vesicles derived from endosomal origin of multivesicular bodies and constitutively released by fusion with the cell membrane. Cancer- secreted exosomes mediate inter-cellular communication, repress host’s immunity and remodel the microenvironment to facilitate tumor metastasis. We propose gastric cancer (GC) -secreted exosomes promote lymphatic metastasis by transporting modulators to the lymph nodes. First, we collect primary GC tissue, tumor-draining lymph nodes (TDLN) and plasma exosomes. The expression of cytokines (IL-6、TNF、PD-L1), metalloproteases, and oncogenes in these specimen will be analyzed. The results will be correlated with the pathological staging of GC. The role of exosomes as a prognostic factor of GC will be studied. Second, we will co-culture the GC-secreted exosomes with naïve T- cells, and analyze the ratio of regulatory T cell (Treg) which indicates the degree of immune- suppression induced by GC-secreted exosomes. Third, we use a mouse model to examine the effect of exosomes infusion on peritoneal metastasis. This study will explore the value of using plasma exosome as a prognostic factor in GC patients, and will help developing a new therapy targeting the exosomes to mitigate lymphatic metastasis of gastric cancers.