Li Xiao-Jing, Liu Pai, Tian Wei-Wei, Li Zhi-Feng, Liu Bao-Guo, Sun Jian-Fang
Department of Dermatology, Affiliated Hospital of Hebei University of Engineering, Handan, Hebei 056002, P.R. China.
Department of Dermatology, Jiangxi Province Dermatosis Special Hospital, Nanchang, Jiangxi 330000, P.R. China.
Oncol Lett. 2017 Oct;14(4):4106-4114. doi: 10.3892/ol.2017.6720. Epub 2017 Aug 4.
Malignant melanoma (MM) is a highly malignant skin tumor. The mechanism of MM pathogenesis and its signaling pathways are not well characterized. C-X-C chemokine receptor type 7 (CXCR7) has been reported to regulate cancer cell invasion. The present study sought to investigate the effects of CXCR7 on MM development. First, CXCR7 expression levels were assessed in the skin tumor tissue of patients with MM. Then, CXCR7 small hairpin RNA was used in M14 melanoma cells in a Transwell culture model and in a transplanted mouse model to test the effects of CXCR7. In addition, immunohistochemistry staining, reverse transcription-quantitative polymerase chain reaction and western blotting were used. The results revealed that CXCR7 expression levels were significantly higher in MM tissue compared with squamous cell carcinoma or basal cell carcinoma tissue. Knocking down CXCR7 in M14 cells significantly inhibited cell migration and invasion in the Transwell culture model. Furthermore, CXCR7 knockdown also significantly reduced the transplanted tumor size, weight and vascular number in the mouse model. It was concluded that CXCR7 interacts with C-X-C motif chemokine ligand 12 to activate the chemokine receptor signaling pathway, and to increase melanoma cell migration, invasion and development.
恶性黑色素瘤(MM)是一种高度恶性的皮肤肿瘤。MM的发病机制及其信号通路尚未完全明确。据报道,C-X-C趋化因子受体7(CXCR7)可调节癌细胞的侵袭。本研究旨在探讨CXCR7对MM发展的影响。首先,评估MM患者皮肤肿瘤组织中CXCR7的表达水平。然后,在Transwell培养模型和移植小鼠模型中,将CXCR7小发夹RNA应用于M14黑色素瘤细胞,以测试CXCR7的作用。此外,还采用了免疫组织化学染色、逆转录定量聚合酶链反应和蛋白质印迹法。结果显示,与鳞状细胞癌或基底细胞癌组织相比,MM组织中CXCR7的表达水平显著更高。在Transwell培养模型中,敲低M14细胞中的CXCR7可显著抑制细胞迁移和侵袭。此外,在小鼠模型中,CXCR7基因敲低也显著减小了移植瘤的大小、重量和血管数量。得出的结论是,CXCR7与C-X-C基序趋化因子配体12相互作用,激活趋化因子受体信号通路,并增加黑色素瘤细胞的迁移、侵袭和发展。