Wang Ting, Han Shuai, Wu Zhipeng, Han Zhitao, Yan Wangjun, Liu Tielong, Wei Haifeng, Song Dianwen, Zhou Wang, Yang Xinghai, Xiao Jianru
Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
Biochem Biophys Res Commun. 2015 Aug 21;464(2):635-41. doi: 10.1016/j.bbrc.2015.06.175. Epub 2015 Jul 9.
Bone metastasis occurs in approximately 30-40% patients with advanced non-small cell lung cancer (NSCLC), but the mechanism underlying this bone metastasis remains poorly understood. The chemokine super family is believed to play an important role in tumor metastasis in lung cancer. The chemokine receptor XCR1 has been identified to promote cell proliferation and migration in oral cancer and ovarian carcinoma, but the role of XCR1 in lung cancer has not been reported. In this study, we demonstrated for the first time that XCR1 was overexpressed in lung cancer bone metastasis as compared with that in patients with primary lung cancer. In addition, the XCR1 ligand XCL1 promoted the proliferation and migration of lung cancer cells markedly, and knockdown of XCR1 by siRNA abolished the effect of XCL1 in cell proliferation and migration. Furthermore, we identified JAK2/STAT3 as a novel downstream pathway of XCR1, while XCL1/XCR1 increased the mRNA level of the downstream of JAK2/STAT3 including PIM1, JunB, TTP, MMP2 and MMP9. These results indicate that XCR1 is a new potential therapeutic target for the treatment of lung cancer bone metastasis.
约30%-40%的晚期非小细胞肺癌（NSCLC）患者会发生骨转移，但这种骨转移的潜在机制仍知之甚少。趋化因子超家族被认为在肺癌的肿瘤转移中起重要作用。趋化因子受体XCR1已被证实可促进口腔癌和卵巢癌的细胞增殖与迁移，但XCR1在肺癌中的作用尚未见报道。在本研究中，我们首次证明与原发性肺癌患者相比，XCR1在肺癌骨转移中高表达。此外，XCR1配体XCL1显著促进肺癌细胞的增殖和迁移，而通过小干扰RNA（siRNA）敲低XCR1可消除XCL1对细胞增殖和迁移的影响。此外，我们确定JAK2/STAT3是XCR1的一条新的下游通路，而XCL1/XCR1可增加JAK2/STAT3下游包括PIM1、JunB、TTP、MMP2和MMP9的mRNA水平。这些结果表明，XCR1是治疗肺癌骨转移的一个新的潜在治疗靶点。
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