Elevated serum CXCL16 is an independent predictor of poor survival in ovarian cancer and may reflect pro-metastatic ADAM protease activity.
Elevated serum CXCL16 is an independent predictor of poor survival in ovarian cancer and may reflect pro-metastatic ADAM protease activity.
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DOI：
10.1038/bjc.2014.55
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发表时间：
2014-03-18
影响因子：
8.8
通讯作者：
Bremer, E.
中科院分区：
文献类型：
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作者：
Gooden, M. J. M.;Wiersma, V. R.;Boerma, A.;Leffers, N.;Boezen, H. M.;ten Hoor, K. A.;Hollema, H.;Walenkamp, A. M. E.;Daemen, T.;Nijman, H. W.;Bremer, E.
在某些癌症中，CXCL 16及其受体CXCR 6的表达与淋巴细胞浸润相关，可能有助于抗肿瘤免疫应答。在其他癌症中，CXCL 16和CXCR 6与促转移活性相关。在本研究中，我们的目的是确定CXCL 16，sCXCL 16和CXCR 6在卵巢癌（OC）中的作用。在包含306个OC患者样本的组织微阵列上分析CXCL 16/CXCR 6表达。采用ELISA法检测118例患者治疗前血清sCXCL 16水平。在体外，用ADAM-10/ADAM-17抑制剂（TAPI-2）和ADAM-10特异性抑制剂（GI 254023 x）处理（原代）OC细胞，然后在细胞膜上（免疫荧光分析，蛋白质印迹）和培养上清液中（ELISA）评价CXCL 16水平。此外，使用划痕试验评估细胞迁移。sCXCL 16独立预测生存率差（风险比=2.28，95%置信区间=1.29-4.02，P=0.005），而CXCL 16和CXCR 6表达均与生存率无关。此外，CXCL 16/CXCR 6表达和血清sCXCL 16水平与淋巴细胞浸润无关。在体外抑制ADAM-17和ADAM-10，但特别是后者，减少CXCL 16膜脱落和强烈减少A2780和培养的原代OC衍生的恶性细胞的细胞迁移。高血清sCXCL 16是OC患者生存不良的预后标志物，可能反映了ADAM-10和ADAM-17的促转移活性。因此，血清sCXCL 16水平可能是识别高转移性肿瘤患者的假标志物。
In certain cancers, expression of CXCL16 and its receptor CXCR6 associate with lymphocyte infiltration, possibly aiding anti-tumour immune response. In other cancers, CXCL16 and CXCR6 associate with pro-metastatic activity. In the current study, we aimed to characterise the role of CXCL16, sCXCL16, and CXCR6 in ovarian cancer (OC). CXCL16/CXCR6 expression was analysed on tissue microarray containing 306 OC patient samples. Pre-treatment serum sCXCL16 was determined in 118 patients using ELISA. In vitro, (primary) OC cells were treated with an ADAM-10/ADAM-17 inhibitor (TAPI-2) and an ADAM-10-specific inhibitor (GI254023x), whereupon CXCL16 levels were evaluated on the cell membrane (immunofluorescent analysis, western blots) and in culture supernatants (ELISA). In addition, cell migration was assessed using scratch assays. sCXCL16 independently predicted for poor survival (hazard ratio=2.28, 95% confidence interval=1.29–4.02, P=0.005), whereas neither CXCL16 nor CXCR6 expression correlated with survival. Further, CXCL16/CXCR6 expression and serum sCXCL16 levels did not associate with lymphocyte infiltration. In vitro inhibition of both ADAM-17 and ADAM-10, but especially the latter, decreased CXCL16 membrane shedding and strongly reduced cell migration of A2780 and cultured primary OC-derived malignant cells. High serum sCXCL16 is a prognostic marker for poor survival of OC patients, possibly reflecting ADAM-10 and ADAM-17 pro-metastatic activity. Therefore, serum sCXCL16 levels may be a pseudomarker that identifies patients with highly metastatic tumours.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
趋化因子网络在卵巢癌发展和发展中的作用：潜在的新型药理靶标。
影响因子：
--
作者：
Barbieri, Federica;Bajetto, Adriana;Florio, Tullio
通讯作者：
Florio, Tullio
影响因子：
3.7
作者：
Matsushita, Kohei;Toiyama, Yuji;Kusunoki, Masato
通讯作者：
Kusunoki, Masato
影响因子：
82.9
作者：
Kononen, J;Bubendorf, L;Kallioniemi, OP
通讯作者：
Kallioniemi, OP
影响因子：
4.4
作者：
Abel, S;Hundhausen, C;Ludwig, A
通讯作者：
Ludwig, A