Macrophages are Recruited to Hypoxic Tumor Areas and Acquire a Pro-Angiogenic M2-Polarized Phenotype via Hypoxic Cancer Cell Derived Cytokines Oncostatin M and Eotaxin
IR@CDRI: CSIR-Central Drug Research Institute, Lucknow
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| Creator |
Tripathi, Chakrapani
Tewari, B N Kanchan, R K Baghel, K S Nautiyal, Naveen Shrivastava, Richa Kaur, Harbeer Bhatt, M L B Bhadauria, Smrati |
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| Date |
2014-12-04T09:18:54Z
2014-12-04T09:18:54Z 2014 |
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| Identifier |
Oncotarget 2014, 5(14), 5350-68
http://hdl.handle.net/123456789/1424 |
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| Description |
TAMs, a unique and distinct M2-skewed myeloid population of tumor stroma, exhibiting pro-tumor functions is fast emerging as a potential target for anti-cancer immunotherapy. Macrophage-recruitment and M2-polarization represent key TAMs-related phenomenon that are amenable to therapeutic intervention. However successful translation of these approaches into effective therapeutic regimen requires better characterization of tumor-microenvironment derived signals that regulate macrophage recruitment and their polarization. Owing to hypoxic milieu being a persistent feature of tumor-microenvironment and a major contributor to malignancy and treatment resistance, the current study was planned with an aim to decipher tumor cell responses to hypoxia vis-a-vis macrophage homing and phenotype switching. Here, we show that hypoxia-primed cancer cells chemoattract and polarize macrophages to pro-angiogenic M2-polarized subtype via Eotaxin and Oncostatin M. Concordantly, hypoxic regions of human breast-cancer specimen exhibited elevated Eotaxin and Oncostatin M levels with concurrently elevated M2-macrophage content. Blockade of Eotaxin/Oncostatin M not only prevented hypoxic breast-cancer cells from recruiting and polarizing macrophages towards an M2-polarized phenotype and retarded tumor progression in BalbC/4T1-syngenic-mice-model of breast-cancer but also enhanced the efficacy of anti-angiogenic Bevacizumab. The findings established these two cytokines as novel targets for devising effective anticancer therapy particularly for tumors that are refractory or develop resistance to anti-angiogenic therapeutics.
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3016276 bytes
application/pdf |
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| Language |
en
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| Relation |
CSIR-CDRI Communication No. 8714
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| Subject |
Hypoxia
M2Polarization TAM Tumor-microenvironment Chemoattract Pro-angiogenic Breast Cancer |
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| Title |
Macrophages are Recruited to Hypoxic Tumor Areas and Acquire a Pro-Angiogenic M2-Polarized Phenotype via Hypoxic Cancer Cell Derived Cytokines Oncostatin M and Eotaxin
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Article
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