Expression of the CXCL12/CXCR4 and CXCL16/CXCR6 axes in cervical intraepithelial neoplasia and cervical cancer.
Expression of the CXCL12/CXCR4 and CXCL16/CXCR6 axes in cervical intraepithelial neoplasia and cervical cancer.
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DOI：
10.5732/cjc.012.10063
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发表时间：
2013-05
影响因子：
--
通讯作者：
Zheng Y
中科院分区：
文献类型：
--
作者：
Huang Y;Zhang J;Cui ZM;Zhao J;Zheng Y
趋化因子CXCL12在妇科肿瘤中高度表达，并在肿瘤生长和扩散中发挥生物学相关作用。最近的证据表明，CXCL16是一种新的趋化因子，在炎症相关肿瘤中过度表达，并介导前列腺癌炎症的致瘤作用。因此，我们分析了CXCL12和CXCL16及其受体CXCR4和CXCR6在宫颈上皮内瘤变（CIN）和宫颈癌中的表达，并进一步评估了它们与临床病理特征和预后的关系。采用组织芯片技术和免疫组化技术分析CXCL12、CXCR4、CXCL16、CXCR6在21例宫颈健康组织、65例宫颈癌组织和60例宫颈癌组织中的表达。分析蛋白表达与临床病理特征和总生存率的关系。这四种蛋白在肿瘤上皮细胞的膜和细胞质中均可见，且随着肿瘤病变从CIN1、CIN2、CIN3向浸润性癌的进展，其分布和表达强度增加。此外，CXCR4的表达与宫颈癌的组织学分级显著相关，而CXCR6的表达与淋巴结转移显著相关。Kaplan-Meier分析显示，CXCR6高表达患者的总生存期明显短于CXCR6低表达患者。CXCL12/CXCR4和CXCL16/CXCR6在CIN和宫颈癌中的共表达水平升高表明宫颈癌的发展是一个持续的过程。此外，CXCR6可能作为宫颈癌的生物标志物和有价值的预后因素。
The chemokine CXCL12 is highly expressed in gynecologic tumors and is widely known to play a biologically relevant role in tumor growth and spread. Recent evidence suggests that CXCL16, a novel chemokine, is overexpressed in inflammation-associated tumors and mediates pro-tumorigenic effects of inflammation in prostate cancer. We therefore analyzed the expression of CXCL12 and CXCL16 and their respective receptors CXCR4 and CXCR6 in cervical intraepithelial neoplasia (CIN) and cervical cancer and further assessed their association with clinicopathologic features and outcomes. Tissue chip technology and immunohistochemistry were used to analyze the expression of CXCL12, CXCR4, CXCL16, and CXCR6 in healthy cervical tissue (21 cases), CIN (65 cases), and cervical carcinoma (60 cases). The association of protein expression with clinicopathologic features and overall survival was analyzed. These four proteins were clearly detected in membrane and cytoplasm of neoplastic epithelial cells, and their distribution and intensity of expression increased as neoplastic lesions progressed through CIN1, CIN2, and CIN3 to invasive cancer. Furthermore, the expression of CXCR4 was associated significantly with the histologic grade of cervical carcinoma, whereas the expression of CXCR6 was associated significantly with lymph node metastasis. In Kaplan-Meier analysis, patients with high CXCR6 expression had significantly shorter overall survival than did those with low CXCR6 expression. The elevated co-expression levels of CXCL12/CXCR4 and CXCL16/CXCR6 in CIN and cervical carcinoma suggest a durative process in cervical carcinoma development. Moreover, CXCR6 may be useful as a biomarker and a valuable prognostic factor for cervical cancer.
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影响因子：
3.8
作者：
Machelon V;Gaudin F;Camilleri-Broët S;Nasreddine S;Bouchet-Delbos L;Pujade-Lauraine E;Alexandre J;Gladieff L;Arenzana-Seisdedos F;Emilie D;Prévot S;Broët P;Balabanian K
通讯作者：
Balabanian K
影响因子：
6.4
作者：
Kajiyama, Hiroaki;Shibata, Kiyosumi;Kikkawa, Fumitaka
通讯作者：
Kikkawa, Fumitaka
影响因子：
4.4
作者：
Abel, S;Hundhausen, C;Ludwig, A
通讯作者：
Ludwig, A
DOI：
10.1111/j.1525-1438.2007.00786.x
发表时间：
2007-03-01
影响因子：
4.8
作者：
Zhang, J. -P.;Lu, W. -G.;Xie, X.
通讯作者：
Xie, X.
影响因子：
6
作者：
Jaafar, Fatimah;Righi, Elda;Poznansky, Mark C.
通讯作者：
Poznansky, Mark C.