CXCR7 參與CXCL12 引發口腔癌細胞的增生效應

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Title:	CXCR7 參與CXCL12 引發口腔癌細胞的增生效應 CXCR7 Involved in CXCL12-induced Proliferation in Oral Squamous Cell Carcinoma
Authors:	林志軒;Jhih-Syuan Lin
Contributors:	健康照護學院醫學檢驗生物技術學系碩士班
Keywords:	口腔癌;趨化激素受體4;趨化激素受體7;趨化激素12;增生;oral cancer;CXCR4;CXCR7;CXCL12;proliferation
Date:	2010
Issue Date:	2010-09-29 12:10:38 (UTC+8)
Abstract:	CXCR7，又稱RDC1，最近才被發現是CXCL12 第二個接受器，它的表現和淋巴癌、肝癌、膀胱癌、前列腺癌的病理變化有相關性。CXCR4，起初被認定是CXCL12 的唯一接受器。CXCL12/CXCR4 和癌細胞的轉移和增生有關，此次研究主要探討CXCR7 和CXCR4 兩個接受器在口腔癌中所扮演的角色。首先我們利用免疫切片染色檢測了58 個病人組織切片，發現CXCR7 的表達與口腔癌具有高度相關性，呈現陽性比例者高達88％(51/58)。以RT-PCR 檢測七株口腔癌細胞株，發現其中 Ca9-22、HSC-3、SAS、Cal-27、SCC4 和TW2.6 細胞有表達，同時利用FACS 檢測CXCR7 蛋白發現Ca9-22，HSC3 和TW2.6 有明顯表達。接著探測CXCL12 對口腔癌細胞的影響，發現在100 ng/mL 濃度下對癌細胞具有刺激增生效果，且此增生作用會受到CXCR7 和CXCR4 的抗體所抑制，以前者抑制效果較大。以上結果顯示，CXCL12 會刺激口腔癌細胞的增生，而它的兩個受體CXCR7 和CXCR4 可能都扮演相當重要的角色，如果同時抑制CXCR7 和CXCR4 則可以達到很強的抑制細胞增生的效果，因此，未來在口腔癌的治療方法上，可以思考同時抑制這兩個接受器的方式來達到最好療效。 CXCR7, formerly called RDC1, is a recently described second receptor for the chemokine CXCL12. CXCR7 expression is correlated with tumor aggressiveness in lymph node, liver, bladder, and prostate cancers. Previously, CXCR4 is the only known natural receptor for CXCL12. Moreover, CXCL12/CXCR4 signaling have been implicated in tumor cell metastasis and proliferation. In this study, we investigate the potential role of CXCR7 and CXCR4 in oral cancer. From examining 58 samples of OSCC (oral squamous cell carcinoma) tissues by immuohistochemical staining, we found that 88%(51/58) cases expressed chemokine receptor CXCR7. Using RT-PCR method, we observed that CXCR7 mRNA was strongly expressed in Ca9-22, HSC-3, SAS, Cal-27, SCC4, and TW-2.6 oral cancer cell lines. At the same time, we detected CXCR7 protein by flow cytometry, and observed that CXCR7 protein was strongly expressed in Ca9-22, HSC3 and TW2.6. CXCL12 can induce cellular proliferation effect at the concentration of 100 ng/mL. And the proliferation-induction effect in OSCC cells were inhibited after treatment with CXCR7 and/or CXCR4 antibodies. CXCR7 antibodies induce stronger inhibition effect than CXCR4’s. Collectively, these results show that CXCL12 play an important role in cellular proliferation in OSCC. CXCR7 and CXCR4 are simultaneously involved in the CXCL12-induced proliferation effect. So, inhibition of both CXCR7 and CXCR4 receptors may be considered a better strategy in treatment for oral cancer.
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