SDF-1及CXC4在口腔鱗狀上皮細胞癌之癌化過程所扮演的角色; Potential role of SDF-1 and CXCR4 in the tumorigenesis of oral squamous cell carcinoma

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Title:	SDF-1及CXC4在口腔鱗狀上皮細胞癌之癌化過程所扮演的角色;Potential role of SDF-1 and CXCR4 in the tumorigenesis of oral squamous cell carcinoma
Authors:	陳佳玉;Chia-Yu Chen
Contributors:	中國醫藥大學：醫學檢驗生物技術學系碩士班
Keywords:	趨化激素;口腔鱗狀上皮細胞癌;Chemokine;oral squamous cell carcinoma
Date:	2007-07-13
Issue Date:	2009-08-12 17:10:00 (UTC+8)
Abstract:	口腔癌發生率居全國癌症第四位，每年新增罹病人口達3000人之多，在台灣也是最快速成長癌症之ㄧ。趨化激素(chemokine)是ㄧ群可調控細胞遷移的發炎小分子(約8~14 kDa)， Stromal cell-derived factor-1 (SDF-1)是趨化激素CXC家族的ㄧ員，它對於血球細胞有強烈的化學趨化作用並刺激細胞的生長發育。有許多文獻指出，SDF-1及其受器Chemokine Receptor-4 (CXCR4) 在許多癌症的致癌過程中扮演著重要的角色。據此觀念，我們著手探討SDF-1或CXCR4是否與口腔癌相關,並探究SDF-1或CXCR4在口腔癌的癌化過程中所扮演的角色。首先我們利用免疫組織化學染色(Immunohistochemical staining)偵測臨床口腔癌組織，發現有相當高比例病人的癌組織中表達SDF-1和受體CXCR4，雖然強度和有表達之癌細胞所佔比率不同。六株口腔癌細胞株也強烈表現CXCR4蛋白，其中由台灣培育出之口腔癌細胞株TW2.6也同時表達SDF-1。再者，口腔癌細胞株經SDF-1作用後，除了促進細胞增生(proliferation)能力外，也增強口腔癌細胞之轉移(migration)以及侵潤(invasion)的能力。以上實驗結果暗示，在口腔癌的致癌過程中SDF-1/CXCR4扮演著相當重要且多重的角色。未來，SDF-1/CXCR4在口腔癌癌化之機制將繼續被探索，同時測試CXCR4的佶抗劑AMD3100是否可抑制腫瘤細胞的生長和轉移,以尋求臨床上治療口腔癌新藥。 Oral cancer is the fourth most common cancer reported nationwide, with an estimated 3000 new cases annually. Chemokines are a group of small (8-14 kDa) pro-inflammatory molecules that can regulate cell trafficking. Stromal cell-derived factor-1 (SDF-1) is a member of CXC chemokine family and also a potent chemoattractant for hematopoietic cells. Many studies implicated that, in many kinds of cancers, SDF-1 act with its specific receptor CXCR4 may play an important role in tumorigenesis process. Based on this conception, we started to investigate the relationship between SDF-1/CXCR4 and oral squamous cell carcinoma (OSCC), and also explore what role does SDF-1/CXCR4 signaling route play in the tumorigenesis of OSCC. First, we observed that CXCR4 and SDF-1 proteins are expressed in OSCC tissues of clinical oral cancer patients in a high ratio circumstances through immunohistochemical staining. CXCR4 was also expressed in all six OSCC cell lines we investigated. TW2.6 cell line, which was established from Taiwan, also expressed SDF-1 proteins. SDF-1 treatment not only enhanced the proliferation ability but also increased migration and invasion activities in these OSCC cell lines. Collectively, these results imply that the SDF-1/CXCR4 axis may play important and multiple roles in the tumorigenesis of OSCC. In the future, the tumorigenesis mechanism of SDF-1/CXCR4 in oral cancer will be investigated continually. Furthermore, the CXCR4 antagonist, AMD3100, will be tested whether it has the ability to inhibit the growth and metastasis of tumor cells. It may be considered as a potential strategy of the therapy for OSCC patients.
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