Absence of CCR2 reduces spontaneous intestinal tumorigenesis in the Apc Min /+ mouse model

The biological activities of chemokine (C-C motif) ligand 2 (CCL2) are mediated via C-C chemokine receptor-2 (CCR2). Increased CCL2 level is associated with metastasis of many cancers. In our study, we investigated the role of the CCL2/CCR2 axis in the development of spontaneous intestinal tumorigen...

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Bibliographic Details
Published in:International journal of cancer 2021-05, Vol.148 (10), p.2594-2607
Main Authors: Jala, Venkatakrishna Rao, Bodduluri, Sobha Rani, Ghosh, Sweta, Chheda, Zinal, Singh, Rajbir, Smith, Michelle E, Chilton, Paula M, Fleming, Christopher J, Mathis, Steven Paul, Sharma, Rajesh Kumar, Knight, Rob, Yan, Jun, Haribabu, Bodduluri
Format: Article
Language:English
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Summary:The biological activities of chemokine (C-C motif) ligand 2 (CCL2) are mediated via C-C chemokine receptor-2 (CCR2). Increased CCL2 level is associated with metastasis of many cancers. In our study, we investigated the role of the CCL2/CCR2 axis in the development of spontaneous intestinal tumorigenesis using the Apc mouse model. Ablation of CCR2 in Apc mice significantly increased the overall survival and reduced intestinal tumor burden. Immune cell analysis showed that CCR2 Apc mice exhibited significant reduction in the myeloid cell population and increased interferon γ (IFN-γ) producing T cells both in spleen and mesenteric lymph nodes compared to Apc mice. The CCR2 Apc tumors showed significantly reduced levels of interleukin (IL)-17 and IL-23 and increased IFN-γ and Granzyme B compared to Apc tumors. Transfer of CCR2 Apc CD4 T cells into Rag2 mice led to development of colitis phenotype with increased CD4 T cells hyper proliferation and IL-17 production. In contrast, adoptive transfer of CCR2 Apc CD4 T cells into Rag2 mice failed to enhance colonic inflammation or IL-17 production. These results a suggest novel additional role for CCR2, where it regulates migration of IL-17 producing cells mediating tumor-promoting inflammation in addition to its role in migration of tumor associated macrophages.
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.33477