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.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Moraes LA,Kar S,Foo SL,Gu T,Toh YQ,Ampomah PB,Sachaphibulkij K,Yap G,Zharkova O,Lukman HM,Fairhurst AM,Kumar AP,Lim LHKdoi
10.1038/s41598-017-17622-5subject
Has Abstractpub_date
2017-12-20 00:00:00pages
17925issue
1issn
2045-2322pii
10.1038/s41598-017-17622-5journal_volume
7pub_type
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