CXC Chemokine Receptors in the Tumor Microenvironment and an Update of Antagonist Development
Chemokine receptors, a diverse group within the seven-transmembrane G protein-coupled receptor superfamily, are frequently overexpressed in malignant tumors. Ligand binding activates multiple downstream signal transduction cascades that drive tumor growth
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CXC Chemokine Receptors in the Tumor Microenvironment and an Update of Antagonist Development Yang Xun, Hua Yang, Jiekai Li, Fuling Wu, and Fang Liu
Contents 1 Introduction 2 CXCR1 and CXCR2 2.1 Cell Signaling Induced by CXCR1 and CXCR2 2.2 CXCR1 and CXCR2 in Tumor Cells 2.3 CXCR1 and CXCR2 in Immune Cells 2.4 Antagonist Development Targeting CXCR1 and CXCR2 3 CXCR3 3.1 CXCR3 Structure and Signaling Mechanisms 3.2 Autocrine and Paracrine Mechanisms of CXCR3 3.3 Antagonists Targeting CXCR3 4 CXCR4 4.1 CXCR4 Signaling 4.2 CXCR4 Expression and Signaling in Tumor Cells 4.3 Association Between CXCR4 and Leukocyte Trafficking 4.4 Antagonists Targeting CXCR4 5 CXCR5 5.1 CXCR5 Expression Patterns 5.2 CXCR5 in Tumor Cells 5.3 CXCR5 in Immune Cells 5.4 Absence of Antagonists Targeting CXCR5 6 CXCR6 6.1 Expression of CXCR6 6.2 CXCR6–TM-CXCL16 and CXCR6–sCXCL16 Axes 6.3 CXCR6 Expression by Tumor Cells 6.4 Association Between CXCR6 and Immune Cells
Yang Xun and Hua Yang contributed equally to this work. Y. Xun, H. Yang, J. Li, and F. Liu (*) Department of Basic Medicine and Biomedical Engineering, School of Stomatology and Medicine, Foshan University, Foshan, Guangdong Province, China e-mail: [email protected] F. Wu Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China
Y. Xun et al. 6.5 Absence of Antagonist Targeting CXCR6 7 CXCR7 7.1 CXCR7 Signaling 7.2 CXCR7 in Tumor Cells 7.3 CXCR7 and Drug Resistance 7.4 Crosstalk of CXCR7 with CXCR3 and CXCR4 7.5 Antagonist Development Targeting CXCR7 8 Concluding Remarks References
Abstract Chemokine receptors, a diverse group within the seven-transmembrane G protein-coupled receptor superfamily, are frequently overexpressed in malignant tumors. Ligand binding activates multiple downstream signal transduction cascades that drive tumor growth and metastasis, resulting in poor clinical outcome. These receptors are thus considered promising targets for anti-tumor therapy. This article reviews recent studies on the expression and function of CXC chemokine receptors in various tumor microenvironments and recent developments in cancer therapy using CXC chemokine receptor antagonists. Keywords CXC antagonists · CXC chemokine receptors · Tumor microenvironment
Abbreviations ADAM10 Akt AML CCRCC CLL CRPC CTL CXCR DLBCL ECM EGFR EMT ERK HCC HER2 HIV IgG IL JNK MAPK MDSC
Disintegrin-like metalloproteinase 10 Protein kinase B Acute myeloid leukemia Clear cell renal cell carcinoma Chronic lymphocytic leukemia Castrated-resistant prostate cancer Cytotoxicity T-cell CXC chemokine receptor Diffuse large B-cell lymphoma Extracellular matrix Epidermal growth factor receptor Epithelial-to-mesenchymal transition Extracellular signal-regulated kinase Hepatocellular carcinoma Epidermal growth factor receptor type 2 Human immunodeficiency virus Immunoglobulin G Interleukin c-Jun N-terminal kinases Mitogen-activated protein kinase Myeloid-derived suppressor cells
CXC Chemokine Receptors in the Tumor Microenvironment and an Update of. . .
MMP NHE
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