Zhang Yong, Yang Chao-Qun, Gao Yang, Wang Ce, Zhang Cheng-Lin, Zhou Xu-Hui
Department of Orthopedic Surgery, Zhabei District Central Hospital, Shanghai 200070, P.R. China.
Department of Orthopedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
Oncol Rep. 2014 Sep;32(3):965-72. doi: 10.3892/or.2014.3290. Epub 2014 Jun 25.
CXC chemokine receptor 7 (CXCR7) has been implicated in tumor development and metastasis in multiple malignancies. Yet, the function and molecular mechanisms of CXCR7 in human osteosarcoma (OS) are still unclear. The aim of the present study was to investigate the role of CXCR7 in human OS. The expression of CXCR7 was assessed by immunohistochemical assay using a tissue microarray procedure in 45 cases of OS tissues. A loss‑of-function approach was used to observe the effects of lentiviral vector-mediated CXCR7 siRNA (Lv-siCXCR7) on biological behaviors including proliferative activities and invasive potential, as indicated by MTT and Transwell assays in OS (MG-63 and U-2 OS) cells. The results showed that the expression of CXCR7 protein in OS tissues was significantly increased compared to that in adjacent non-cancerous tissues (68.9 vs. 53.3%, P=0.033), and was correlated with the distant metastasis of the tumors (P=0.004). Knockdown of CXCR7 suppressed proliferation and invasion of OS cells through decreased expression of PI3K, AKT, β-arrestin, proliferating cell nuclear antigen (PCNA), and matrix metalloproteinase-9 (MMP-9). In addition, the tumor volume in U-2 OS subcutaneous tumor models treated with Lv-siCXCR7 was significantly smaller than the tumor volume in the negative control group (P<0.01). Collectively, our findings indicate that upregulation of CXCR7 expression is correlated with distant metastasis of OS, while knockdown of CXCR7 blocks the development of OS cells through inhibition of the PI3K/AKT and β-arrestin pathways, suggesting that CXCR7 may serve as a potential therapeutic target for the treatment of cancer.
CXC趋化因子受体7（CXCR7）已被证明与多种恶性肿瘤的发生发展及转移有关。然而，CXCR7在人类骨肉瘤（OS）中的功能及分子机制仍不清楚。本研究旨在探讨CXCR7在人类骨肉瘤中的作用。采用组织芯片技术，通过免疫组化法检测45例骨肉瘤组织中CXCR7的表达。采用功能丧失方法，观察慢病毒载体介导的CXCR7小干扰RNA（Lv-siCXCR7）对骨肉瘤（MG-63和U-2 OS）细胞增殖活性和侵袭潜能等生物学行为的影响，通过MTT法和Transwell法进行检测。结果显示，骨肉瘤组织中CXCR7蛋白的表达明显高于相邻非癌组织（68.9% 对53.3%，P = 0.033），且与肿瘤的远处转移相关（P = 0.004）。敲低CXCR7可通过降低PI3K、AKT、β-抑制蛋白、增殖细胞核抗原（PCNA）和基质金属蛋白酶-9（MMP-9）的表达来抑制骨肉瘤细胞的增殖和侵袭。此外，Lv-siCXCR7处理的U-2 OS皮下肿瘤模型中的肿瘤体积明显小于阴性对照组（P < 0.01）。综上所述，我们的研究结果表明，CXCR7表达上调与骨肉瘤的远处转移相关，而敲低CXCR7可通过抑制PI3K/AKT和β-抑制蛋白途径来阻断骨肉瘤细胞的发展，提示CXCR7可能是癌症治疗的一个潜在靶点。
