樹突狀細胞DC-SIGN辨認鼻咽癌細胞上醣化Annexin A2

Dendritic cells recognize glycosylated Annexin A2 on nasopharyngeal carcinoma cells through DC-SIGN

許庭睿(Tin-Jui Hsu)

指導教授 ： 陳建和

共同指導教授 ： 林詠峯(Yung-Feng Lin)

臺北醫學大學/醫學科技學院/醫學檢驗暨生物技術學系/碩士(2013年)

https://doi.org/10.6831/TMU.2013.00086

摘要

鼻咽癌是一種盛行於東南亞地區包括台灣的惡性上皮細胞癌。目前治療鼻咽癌主要的方式透過放射性以及化學性治療，但是往往會造成正常組織及細胞的損壞，因此發展鼻咽癌專一性的免疫治療是值得一試的。許多研究中指出樹突狀細胞對於免疫抗癌扮演相當重要的角色，然而樹突狀細胞上的特異性細胞間黏附分子-3-辨認非整合素(DC-SIGN)是樹突狀細胞上一種C型凝集素(C-type lectin)，它可以辨認腫瘤細胞膜上特殊的醣類結構進而調節樹突狀細胞逃避相關免疫機制。在本研究中我們發現鼻咽癌TW01細胞上確實有DC-SIGN可辨認的配體（ligand），當樹突狀細胞被鼻咽癌細胞或內含物處理過後，其免疫抑制性的介白素(IL)-10生產增加並延緩成熟。接下來我們用免疫沈澱法從鼻咽癌細胞上找到了DC-SIGN的可能配體annexin A2。當annexin A2的表達或功能被阻斷時，鼻咽癌細胞對DC-SIGN的結合能力和樹突狀細胞生產IL-10的能力都下降了，這表示鼻咽癌細胞對樹突狀細胞的免疫抑制調控是特異地透過DC-SIGN和annexin A2的交互作用。最後我們發現鼻咽癌細胞上的annexin A2和其它含甘露醣的N-乙醯聚醣對於DC-SIGN的活化相當重要。Annexin A2是鼻咽癌免疫治療上很有潛力的腫瘤標的。

關鍵字

鼻咽癌 ； 樹突狀細胞 ； 樹突狀細胞上的特異性細胞間黏附分子-3-辨認非整合素

並列摘要

NPC is an epithelial cell-derived malignant tumor that mainly occurs in Southeast Asia including Taiwan. Radiotherapy and chemotherapy are the primary treatments of nasopharyngeal cancer, but normal tissues are usually affected with various side effects. There is an unmet medical need to develop a therapeutic method to distinguish cancer cells from normal cells. Dendritic cells (DCs) play an essential role in immunity against tumor and can be used as an important tool to conduct cancer immunotherapy. However, DCs also express a C-type lectin, DC-pecific ICAM-3-Grabbing Nonintegrin (DC-SIGN), that can induce suppressive immune responses by recognizing carbohydrate structure. Many studies indicated that cancer cells escape from immunosurveillance by modulating the functions of DCs via DC-SIGN. In this study, we found that DC-SIGN ligands were expressed on NPC cells. When treated with NPC cells or cell components, DCs produced immunosuppressive cytokine IL-10 and immature. Then we performed co-immunoprecipitation and identified annexin A2 on NPC cells as a candidate ligand for DC-SIGN . When annexin A2 was knocked down or blocked in NPC cells, DC-SIGN-binding capacity on NPC cells and IL-10 production in DCs were reduced, suggesting a specific immunosuppressive response of DCs by NPC through DC-SIGN-annexin A2 interactions. Finally we demonstrated that N-glycans on annexin A2 and other mannose-containing DC-SIGN ligands on NPC cells were important for DC-SIGN activity. Annexin A2 is a potential targeting for anti- NPC therapy.

並列關鍵字

Nasopharyngeal carcinoma ； Dendritic cells ； DC-SIGN

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