CCR5/CCL5 axis interaction promotes migratory and invasiveness of pancreatic cancer cells.
CCR5/CCL5 axis interaction promotes migratory and invasiveness of pancreatic cancer cells.
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CCR5/CCL5轴相互作用促进胰腺癌细胞的迁移和侵入性。
DOI：
10.1038/s41598-018-19643-0
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发表时间：
2018-01-22
影响因子：
4.6
通讯作者：
Singh R
中科院分区：
文献类型：
--
作者：
Singh SK;Mishra MK;Eltoum IA;Bae S;Lillard JW Jr;Singh R
胰腺癌（PC）是最致命的癌症之一，由于其侵袭性和转移性，仍然是一个重大挑战。CCR5和CCL5水平的升高已经确立了各种癌症（包括PC）疾病状态的指标。然而，它们在前列腺癌侵袭和转移中的作用尚不清楚。在这里，我们对PC组织进行了免疫组化，发现与非肿瘤组织相比，转移性PC组织中CCR5和CCL5的上皮染色升高。体外流式细胞术、免疫荧光和western blotting对人PC细胞株（AsPc-1、BxPc-3和MIA PaCa-2）进行的实验显示，CCR5的表达水平较高。表达CCR5的PC细胞的CCL5激活增加了其侵袭潜能，而CCR5抑制剂马拉维洛克治疗则抑制了CCL5的激活。CCL5通过F-actin聚合介导PC细胞的增殖，而马拉韦洛克处理后细胞增殖能力明显减弱。CCR5与CCL5的直接相互作用通过钙动员试验得到验证。综上所述，我们的研究结果表明CCR5和CCL5是转移性PC癌的潜在标记物，它们的相互作用导致PC细胞侵袭增加。因此，阻断CCR5/CCL5轴可能有助于预防转移，并为控制PC进展提供更有效的治疗策略。
Pancreatic cancer (PC) is one of the deadliest cancers and remains a major challenge due to its invasive and metastatic nature. Increased levels of CCR5 and CCL5 have established indicators for disease status in various cancers, including PC. However, their role in invasion and metastasis of PC is not known. Here we conducted immunohistochemistry of PC tissues and found elevated epithelial staining for CCR5 and CCL5 in metastatic PC tissues compared to non-neoplastic. In vitro experiments, such as flow cytometry, immunofluorescence and western blotting with human PC cell lines (AsPc-1, BxPc-3 and MIA PaCa-2), showed higher expression levels of CCR5. The CCL5 activation of PC cells expressing CCR5 increased their invasive potential, while treatment with CCR5 inhibitor maraviroc inhibited the CCL5 activation. CCL5 induced proliferation of PC cells was mediated through F-actin polymerization, while there was marked reduction when the cells were treated with maraviroc. The direct interaction of CCR5 with CCL5 was verified using a calcium mobilization assay. Taken together, our results demonstrate that CCR5 and CCL5 are potential markers for metastatic PC cancer, and their interaction leads to the increased PC cell invasion. Thus, blocking CCR5/CCL5 axis might prove beneficial to prevent metastasis and provide a more therapeutic strategy to control PC progression.
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影响因子：
7.3
作者：
Ignatov, A.;Robert, J.;Schaller, H. C.
通讯作者：
Schaller, H. C.
DOI：
10.1016/j.atg.2013.05.004
发表时间：
2013-12-01
期刊：
Applied & translational genomics
影响因子：
--
作者：
Barmania, Fatima;Pepper, Michael S
通讯作者：
Pepper, Michael S
影响因子：
7.5
作者：
Bravo-Cordero, Jose Javier;Hodgson, Louis;Condeelis, John
通讯作者：
Condeelis, John
DOI：
10.2174/138955751513150923094709
发表时间：
2015
期刊：
Mini reviews in medicinal chemistry
影响因子：
--
作者：
Khalid A;Wolfram J;Ferrari I;Mu C;Mai J;Yang Z;Zhao Y;Ferrari M;Ma X;Shen H
通讯作者：
Shen H
影响因子：
4
作者：
Balkwill, Frances R.;Capasso, Melania;Hagemann, Thorsten
通讯作者：
Hagemann, Thorsten