Annexin A2蛋白在鼻咽癌中調控多種惡化表型和治療上的耐受性

鼻咽癌細胞為一種位於鼻咽的惡性上皮細胞癌，其盛行於台灣及東南亞地區。不同於其他頭頸癌，鼻咽癌早期就具有高轉移能力而且晚期之病患，常因其高度侵犯轉移之特性，造成治療之失敗。因此更進一步了解相關分子，將有助於整體治療之成效。先前透過免疫組織化學染色法(IHC)，發現annexin A2蛋白在鼻咽癌病人的腫瘤組織中有較高的表現量，近幾年不同腫瘤研究中也指出annexin A2蛋白質表現與腫瘤惡化相關性，因此進而探討annexin A2在鼻咽癌所扮演的角色。透過基因靜默(gene silence)抑制annexin A2表現，發現抑制annexin A2會降低癌細胞的生長能力，增加細胞對化療藥物 (Cisplatin、5-FU、Vincristine、 Docetaxel)與放射線治療之敏感性。抑制Annexin A2表現會降低細胞移行、黏附和侵犯能力。動物實驗也證實降低annexin A2表現會抑制腫瘤細胞的生長。進一步探討相關調控分子，發現annexin A2會調控上皮-間質細胞轉化（EMT）之相關分子之表現、AKT分子表現與磷酸化現象。在臨床層面分析，發現annexin A2高度表現於晚期鼻咽癌病患且與表現量與N期有相關性。藉由這些研究結果，我們更加了解annexin A2在鼻咽癌細胞的功能，未來annexin A2也許可以當成臨床上治療的一個標的與預後指標。

關鍵字

鼻咽癌； Annexin A2 ； EMT ；化療；放射性治療

並列摘要

Nasopharyngeal carcinoma (NPC), originated from the epithelium of the nasopharynx, is a common malignant tumor. NPC mainly occurs in the Southeast Asia including Taiwan. Characteristically, NPC differs from other head and neck carcinomas, especially for its high metastasis character and poor efficiency of clinical treatment. Recently, many reports have indicated that annexin A2 might regulate the metastasis on different kinds of cancer. However, the tumorigenic function of annexin A2 in NPC is not yet understood. Annexin A2 shRNAs were used to evaluate the effects of annexin A2 suppression on NPCs. Annexin A2 silencing reduces the cell proliferation ability and increase chemotherapeutic drugs (Cisplatin, 5-FU, Vincristine and Docetaxel) and irradiation sensitivity. Moreover, annexin A2 not only up-regulates cell adhesion, migration, and invasion abilities on NPCs, but also involves in epithelial-mesenchymal transition (EMT). These cellular results were confirmed using tumor xenografts in mice, as annexin A2 silencing led to suppress tumor growth. Clinicl study reveals that the high level of annexin A2 on late-staged NPC patient tissues and associated with N stage. In summary, annexin A2 not only regulates many malignant phenotypes such as migration, invasion, adhesion and EMT, but also controls therapeutic tolerance in NPCs. Annexin A2 may serve as prognostic markers and targets in NPC.

並列關鍵字

nasoparyngeal carcinoma (NPC) ； Annexin A2 ； chemotherapy ； radiotherapy ； epithelial-mesenchymal transition (EMT)

參考文獻

1. Cho, W.C., Nasopharyngeal carcinoma: molecular biomarker discovery and progress. Mol Cancer, 2007. 6: p. 1.

2. Chen, C.J., et al., Cancer epidemiology and control in Taiwan: a brief review. Jpn J Clin Oncol, 2002. 32 Suppl: p. S66-81.

3. Sun, L.M., et al., Trends in the incidence rates of nasopharyngeal carcinoma among Chinese Americans living in Los Angeles County and the San Francisco metropolitan area, 1992-2002. Am J Epidemiol, 2005. 162(12): p. 1174-8.

4. Niedobitek, G., A. Agathanggelou, and J.M. Nicholls, Epstein-Barr virus infection and the pathogenesis of nasopharyngeal carcinoma: viral gene expression, tumour cell phenotype, and the role of the lymphoid stroma. Semin Cancer Biol, 1996. 7(4): p. 165-74.

5. Spano, J.P., et al., Nasopharyngeal carcinomas: an update. Eur J Cancer, 2003. 39(15): p. 2121-35.

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Annexin A2蛋白在鼻咽癌中調控多種惡化表型和治療上的耐受性

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