Chemokine receptor CX3CR1 contributes to macrophage survival in tumor metastasis
Open Access
- 18 November 2013
- journal article
- Published by Springer Science and Business Media LLC in Molecular Cancer
- Vol. 12 (1), 141
- https://doi.org/10.1186/1476-4598-12-141
Abstract
Background: Macrophages, the key component of the tumor microenvironment, are differentiated mononuclear phagocyte lineage cells that are characterized by specific phenotypic characteristics that have been implicated in tumor growth, angiogenesis, and invasion. CX3CR1, the chemoattractant cytokine CX3CL1 receptor, plays an important role in modulating inflammatory responses, including monocyte homeostasis and macrophage phenotype and function. However, the role of CX3CR1 in the regulation of the tumor inflammatory microenvironment is not fully understood. Methods: Using in vivo hepatic metastasis model, human colon carcinoma specimens, immunohistochemical staining, TUNEL staining, flow cytometry analysis, Western blotting assay and co-culture in three-dimensional peptide gel, we determined the effects of CX3CR1 on angiogenic macrophage survival and tumor metastasis. Results: In this study, we found that CX3CR1 was expressed in human colon carcinomas in a histologic grade- and stage-dependent manner, and CX3CR1 upregulation in TAMs was correlated with poor prognosis. Furthermore, we showed that in a microenvironment lacking CX3CR1, the liver metastasis of colon cancer cells was significantly inhibited. The underlying mechanism is associated with decrease accumulation of angiogenic macrophages that can be partly attributed to increased apoptosis in the tumor microenvironment, thus leading to impaired tumor angiogenesis in the liver and suppressed tumor metastasis. Conclusions: Our results suggest a role of CX3CR1 in angiogenic macrophage survival in the tumor microenvironment contributing to tumor metastasis.Keywords
This publication has 36 references indexed in Scilit:
- Role of the CX3CL1-CX3CR1 axis in chronic inflammatory lung diseases.2010
- Macrophage Diversity Enhances Tumor Progression and MetastasisCell, 2010
- Tumor-associated macrophages (TAM) as major players of the cancer-related inflammationJournal of Leukocyte Biology, 2009
- Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instabilityCarcinogenesis: Integrative Cancer Research, 2009
- The tumor microenvironment and its contribution to tumor evolution toward metastasisHistochemistry and Cell Biology, 2008
- Microenvironmental regulation of metastasisNature Reviews Cancer, 2008
- The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functionsThe Journal of Experimental Medicine, 2007
- Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaquesJCI Insight, 2007
- TUMOR STROMA AND REGULATION OF CANCER DEVELOPMENTAnnual review of pathology, 2006
- The Inflammatory Tumor Microenvironment and Its Impact on Cancer DevelopmentContributions to microbiology, 2006