Overexpression of CXCR7 accelerates tumor growth and metastasis of lung cancer cells

Respiratory Research

Alex H. Chang¹  Qian Cheng²  Zheng Fang³  Dong-dong Xue⁴  Yan-jun Lei⁵  Wen Wang⁶  Huan Liu⁷  Dong-sheng Xu⁸  Ya Zheng⁹ 

[1] Clinical Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 200438, Shanghai, China;Department of Anesthesiology, Cancer Hospital Affiliated to Fudan University, 200032, Shanghai, China;Department of Anesthesiology, Huadong Hospital Affiliated to Fudan University, 200040, Shanghai, China;Department of Hepatobiliary Surgery, Hebei General Hospital, 050051, Shijiazhuang, China;Department of Immunology and Microbiology, School of Basic Medical Science, Xi’an Jiaotong University Health Science Center, 710061, Xi’an, China;Department of Traditional Chinese Medicine, Xijing Hospital Affiliated to the Fourth Military Medical University, 710032, Xi’an, China;Department of Traditional Chinese Medicine, Xijing Hospital Affiliated to the Fourth Military Medical University, 710032, Xi’an, China;Department of Immunology and Microbiology, School of Basic Medical Science, Xi’an Jiaotong University Health Science Center, 710061, Xi’an, China;Institute of Rehabilitation Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China;Rehabilitation Section, Spine Surgery Division of Department of Orthopedics, Tongji Hospital Affiliated to Tongji University School of Medicine, 200065, Shanghai, China;

关键词: CXCL12/SDF-1;    CXCR4;    CXCR7;    Overexpression;    Invasion;    Metastasis;    Lung cancer;   

DOI  :  10.1186/s12931-020-01518-6

来源: Springer

【 摘 要 】

BackgroundUnder physiological conditions, CXCL12 modulates cell proliferation, survival, angiogenesis, and migration mainly through CXCR4. Interestingly, the newly discovered receptor CXCR7 for CXCL12 is highly expressed in many tumor cells as well as tumor-associated blood vessels, although the level of CXCR7 in normal cells is low. Recently, many studies have suggested that CXCR7 promotes cell growth and metastasis in more than 20 human malignancies, among which lung cancer is the leading cause of cancer-associated deaths worldwide. Thus, the mechanism of CXCR7 in the progression of lung cancer is urgently needed.MethodsFirst, we explored CXCR4 and CXCR7 expression in human lung cancer specimens and cell lines by immunohistochemistry, western blot and flow cytometry. Then, we chose the human lung adenocarcinoma cell line A549 that stably overexpressed CXCR7 through the way of lentivirus-mediated transduction. Next, “wound healing” assay and transwell assay were applied to compare the cell migration and invasion ability, and stripe assay was used to evaluate the cell polarization. Last, our team established a mouse xenograft model of human lung cancer and monitored tumor proliferation and metastasis by firefly luciferase bioluminescence imaging in SCID/Beige mice.ResultsIn clinical lung cancer samples, CXCR7 expression was almost not detected in normal tissue but upregulated in lung tumor tissue, whereas, CXCR4 was highly expressed in both normal and tumor tissues. Furthermore, overexpression of CXCR7 enhanced A549 cell migration and polarization in vitro. Besides, mouse xenograft model of human lung cancer showed that CXCR7 promoted primary lung tumor’s growth and metastasis to the second organ, such as liver or bone marrow in SCID/Beige mice in vivo.ConclusionsThis study describes the multiple functions of CXCR7 in lung cancer. Thus, these results suggest that CXCR7 may be a malignancy marker and may provide a novel target for anticancer therapy.

【 授权许可】

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