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Title: Annexin-A1 enhances breast cancer growth and migration by promoting alternative macrophage polarization in the tumour microenvironment
Authors: Moraes L.A. 
Kar S.
Foo S.L.
Gu T.
Toh Y.Q.
Ampomah P.B.
Sachaphibulkij K. 
Yap G. 
Zharkova O.
Lukman H.M. 
Fairhurst A.-M.
Kumar A.P. 
Lim L.H.K. 
Keywords: annexin A1, mouse
formyl peptide receptor 2, mouse
formylpeptide receptor
immunoglobulin enhancer binding protein
lipocortin 1
mitogen activated protein kinase
cell motion
cell proliferation
experimental mammary neoplasm
signal transduction
tumor cell culture
tumor microenvironment
Annexin A1
Cell Movement
Cell Proliferation
Extracellular Signal-Regulated MAP Kinases
Mammary Neoplasms, Animal
NF-kappa B
Receptors, Formyl Peptide
Signal Transduction
Tumor Cells, Cultured
Tumor Microenvironment
Issue Date: 2017
Publisher: Nature Publishing Group
Citation: Moraes L.A., Kar S., Foo S.L., Gu T., Toh Y.Q., Ampomah P.B., Sachaphibulkij K., Yap G., Zharkova O., Lukman H.M., Fairhurst A.-M., Kumar A.P., Lim L.H.K. (2017). Annexin-A1 enhances breast cancer growth and migration by promoting alternative macrophage polarization in the tumour microenvironment. Scientific Reports 7 (1) : 17925. ScholarBank@NUS Repository.
Abstract: Macrophages are potent immune cells with well-established roles in the response to stress, injury, infection and inflammation. The classically activated macrophages (M1) are induced by lipopolysaccharide (LPS) and express a wide range of pro-inflammatory genes. M2 macrophages are induced by T helper type 2 cytokines such as interleukin-4 (IL4) and express high levels of anti-inflammatory and tissue repair genes. The strong association between macrophages and tumour cells as well as the high incidences of leukocyte infiltration in solid tumours have contributed to the discovery that tumour-associated macrophages (TAMs) are key to tumour progression. Here, we investigated the role of Annexin A1 (ANXA1), a well characterized immunomodulatory protein on macrophage polarization and the interaction between macrophages and breast cancer cells. Our results demonstrate that ANXA1 regulates macrophage polarization and activation. ANXA1 can act dually as an endogenous signalling molecule or as a secreted mediator which acts via its receptor, FPR2, to promote macrophage polarization. Furthermore, ANXA1 deficient mice exhibit reduced tumour growth and enhanced survival in vivo, possibly due to increased M1 macrophages within the tumor microenvironment. These results provide new insights into the molecular mechanisms of macrophage polarization with therapeutic potential to suppress breast cancer growth and metastasis. © 2017 The Author(s).
Source Title: Scientific Reports
ISSN: 2045-2322
DOI: 10.1038/s41598-017-17622-5
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