The chemokine CXCL16 and its receptor, CXCR6, as markers and promoters of inflammation-associated cancers.
The chemokine CXCL16 and its receptor, CXCR6, as markers and promoters of inflammation-associated cancers.
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DOI：
10.1371/journal.pone.0006695
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发表时间：
2009-08-19
期刊：
影响因子：
3.7
通讯作者：
Farber JM
中科院分区：
文献类型：
--
作者：
Darash-Yahana M;Gillespie JW;Hewitt SM;Chen YY;Maeda S;Stein I;Singh SP;Bedolla RB;Peled A;Troyer DA;Pikarsky E;Karin M;Farber JM
临床观察和小鼠模型表明，炎症可能是促肿瘤发生的。由于趋化因子在白细胞运输中至关重要，我们假设趋化因子在炎症相关癌症中起重要作用。在前列腺癌细胞系和异种移植物中筛选37种趋化因子，发现CXCL 16（受体CXCR 6的配体）是表达最一致的趋化因子。121例人前列腺标本的免疫组织化学和/或免疫荧光和共聚焦成像显示，CXCL 16和CXCR 6在前列腺癌细胞和相邻T细胞上共表达。CXCL 16和CXCR 6在癌细胞上的表达水平与包括高分期和高级别在内的不良预后特征相关，并且表达还与癌症间质中的炎后变化相关，如通过α-平滑肌肌动蛋白的损失所揭示的。此外，CXCL 16增强了表达CXCR 6的癌症和原代CD 4 T细胞的生长。我们研究了CXCL 16在另外461个样本中的表达，涵盖了12种肿瘤类型，发现CXCL 16在多种与炎症相关的人类癌症中表达。我们的研究首次描述了CXCL 16/CXCR 6在人类癌细胞和邻近T细胞上的表达，并证明了CXCL 16和CXCR 6与癌症造口的不良预后特征和反应性变化之间的相关性。综上所述，我们的数据表明，CXCL 16和CXCR 6可以标记在炎症环境中产生的癌症，并通过直接影响癌细胞生长和诱导肿瘤相关白细胞的迁移和增殖介导炎症的促肿瘤发生作用。
Clinical observations and mouse models have suggested that inflammation can be pro-tumorigenic. Since chemokines are critical in leukocyte trafficking, we hypothesized that chemokines play essential roles in inflammation-associated cancers. Screening for 37 chemokines in prostate cancer cell lines and xenografts revealed CXCL16, the ligand for the receptor CXCR6, as the most consistently expressed chemokine. Immunohistochemistry and/or immunofluorescence and confocal imaging of 121 human prostate specimens showed that CXCL16 and CXCR6 were co-expressed, both on prostate cancer cells and adjacent T cells. Expression levels of CXCL16 and CXCR6 on cancer cells correlated with poor prognostic features including high-stage and high-grade, and expression also correlated with post-inflammatory changes in the cancer stroma as revealed by loss of alpha-smooth muscle actin. Moreover, CXCL16 enhanced the growth of CXCR6-expressing cancer and primary CD4 T cells. We studied expression of CXCL16 in an additional 461 specimens covering 12 tumor types, and found that CXCL16 was expressed in multiple human cancers associated with inflammation. Our study is the first to describe the expression of CXCL16/CXCR6 on both cancer cells and adjacent T cells in humans, and to demonstrate correlations between CXCL16 and CXCR6 vs. poor both prognostic features and reactive changes in cancer stoma. Taken together, our data suggest that CXCL16 and CXCR6 may mark cancers arising in an inflammatory milieu and mediate pro-tumorigenic effects of inflammation through direct effects on cancer cell growth and by inducing the migration and proliferation of tumor-associated leukocytes.
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影响因子：
11.2
作者：
Meijer, Joost;Ogink, Janneke;Roos, Ed
通讯作者：
Roos, Ed
DOI：
10.1164/rccm.200501-142oc
发表时间：
2005-11-15
影响因子：
24.7
作者：
Agostini, C;Cabrelle, A;Semenzato, G
通讯作者：
Semenzato, G
影响因子：
15.9
作者：
Kim, CH;Kunkel, EJ;Butcher, EC
通讯作者：
Butcher, EC
影响因子：
30.5
作者：
Matloubian, M;David, A;Cyster, JG
通讯作者：
Cyster, JG
DOI：
10.1186/bcr1746
发表时间：
2007
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
DeNardo DG;Coussens LM
通讯作者：
Coussens LM