Annexin A2蛋白在鼻咽癌中調節多種惡性表型並可作為腫瘤進展的指標

Annexin A2 regulates multiple malignant phenotypes and serves as a tumor progression marker in Nasopharyngeal carcinoma

宋宇軒(Yu-Hsuan Sung)

指導教授 ： 陳建和

共同指導教授 ： 鄭朝文(Chao-Wen Cheng)

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.2013.00088

摘要

鼻咽癌是一種盛行於台灣以及東南亞地區的惡性上皮細胞癌，放射性或化學性的鼻咽癌療法是目前最普遍使用的治療方式，但這些方法往往會影響正常組織並產生各種副作用。經由免疫組織化學染色法(IHC)，我們發現Annexin A2蛋白在鼻咽癌的腫瘤組織中有較高的表現量。Annexin A2(ANXA2)蛋白，為ㄧ鈣依賴且磷脂質高結合性的細胞內蛋白質。許多研究已指出， ANXA2蛋白表現的失調與腫瘤的發生、侵襲、癌細胞增生與轉移等惡性表型相關。然而，ANXA2在鼻咽癌中的角色仍不清楚。因此，我們利用在兩株本土的鼻咽癌細胞株(TW01, BM1)以shRNA (Short hairpin RNA)進行剔除(knockdown) ANXA2的基因表現來探討ANXA2在鼻咽癌所扮演的角色，以利進一步尋找新的治療策略。本研究，乃是目前首次在鼻咽癌細胞株進行ANXA2的基因靜默，我們發現降低ANXA2能夠抑制鼻咽癌細胞株的移動力, 存活力, 血管管柱形成以及自我吞噬的能力。我們也發現在NPC中，ANXA2有助於以TGF-β誘導的EMT現象。此外我們還發現以shRNA knockdown ANXA2的鼻咽癌細胞異體移植於嚴重免疫缺陷鼠(NSG)有強力抗腫瘤影響，能顯著的抑制腫瘤生長。這些發現暗示ANXA2在鼻咽癌中可調控許多惡性表型，可作為鼻咽癌腫瘤進展的指標。

關鍵字

Annexin A2 ； 鼻咽癌 ； 上皮細胞間質轉型 ； 免疫組織化學染色法 ； 動物模型

並列摘要

NPC (Nasopharyngeal carcinoma) is an epithelial cell-derived malignant tumor that mainly occurs in Southeast Asia including Taiwan. Radiotherapy and chemotherapy are well-established standard procedures in current treatment of various neoplasms, but normal tissues are also affected and cause various side effects. We found the expression of Annexin A2 in clinical NPC tissue was highly expressed by IHC (Immunohistochemistry). Annexin A2 (ANXA2), a calcium-dependent phospholipids-binding high-abundant intracellular protein. Accumulated evidences indicated that ANXA2 deregulation was associated with the occurrence, invasion, proliferation and metastasis of cancers. The role of ANXA2 in NPC is unclear. Therefore, we knockdown ANXA2 by shRNA transfection in two Taiwan local NPC cell lines (TW01 and BM1) and we would like to investigate the role of ANXA2 in NPC, and hope it could provide a new therapy strategy against NPC. In this study, we are the first to establish the ANXA2 silencing cells in NPC, our data shows that knockdown of ANXA2 inhibits cell migration, viability, vascular tube formation, autophagy. We also found that ANXA2 contributes to TGF-β-induced epithelial-mesenchymal transition of NPC cells. In addition, we further found that direct knockdown ANXA2 expression by shRNA transfection renders potent antitumor effects, with significant inhibition of xenografted tumor growth in situ. These findings suggest that ANXA2 regulates multiple malignant phenotypes and could serve as a tumor progression marker in NPC.

並列關鍵字

Annexin A2 ； Nasopharyngeal carcinoma ； Epithelial to mesenchymal transition ； Immunohistochemistry ； animal model

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