A C-X-C Chemokine Receptor Type 2-Dominated Cross-talk between Tumor Cells and Macrophages Drives Gastric Cancer Metastasis

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Zhijun ZhouChanghua Zhang

Abstract

C-X-C chemokine receptor type 2 (CXCR2) is a key regulator that drives immune suppression and inflammation in tumor microenvironment. CXCR2-targeted therapy has shown promising results in several solid tumors. However, the underlying mechanism of CXCR2-mediated cross-talk between gastric cancer cells and macrophages still remains unclear.Experimental Design: The expression of CXCR2 and its ligands in 155 human gastric cancer tissues was analyzed via immunohistochemistry, and the correlations with clinical characteristics were evaluated. A coculture system was established, and functional assays, including ELISA, transwell, cell viability assay, and qPCR, were performed to determine the role of the CXCR2 signaling axis in promoting gastric cancer growth and metastasis. A xenograft gastric cancer model and a lymph node metastasis model were established to study the function of CXCR2 in vivo. CXCR2 expression is associated with the prognosis of patients with gastric cancer (P = 0.002). Of all the CXCR2 ligands, CXCL1 and CXCL5 can significantly promote migration of gastric cancer cells. Macrophages are the major sources of CXCL1 and CXCL5 in the gastric cancer microenvironment, and promote migration of gastric cancer cells through ...Continue Reading

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Citations

Feb 23, 2020·The Journal of Pathology·Tim Beltraminelli, Michele De Palma
Sep 11, 2019·Cold Spring Harbor Perspectives in Medicine·Asmaa El-KenawiBrian Ruffell
Sep 2, 2020·International Journal of Molecular Sciences·Ala Litman-ZawadzkaBarbara Mroczko
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Jan 20, 2021·Clinical and Translational Medicine·Neng WangZhiyu Wang
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Nov 14, 2020·International Journal of Molecular Sciences·Elzbieta PawluczukBarbara Mroczko
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Jun 3, 2021·International Journal of Molecular Sciences·Sana HibinoKoji Taniguchi
Jul 8, 2021·Nature Reviews. Immunology·Catherine C Hedrick, Ilaria Malanchi

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