Annexin-A1 enhances breast cancer growth and migration by promoting alternative macrophage polarization in the tumour microenvironment
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...
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Published in | Scientific reports Vol. 7; no. 1; pp. 17925 - 12 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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England
Nature Publishing Group
20.12.2017
Nature Publishing Group UK |
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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. |
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AbstractList | 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. 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. 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. |
ArticleNumber | 17925 |
Author | Kumar, Alan Prem Foo, Sok Lin Toh, Yi Qian Zharkova, Olga Yap, Gracemary Ampomah, Patrick B Lim, Lina H K Lukman, Hakim M Kar, Shreya Gu, Tong Moraes, Leonardo A Fairhurst, Anna-Marie Sachaphibulkij, Karishma |
Author_xml | – sequence: 1 givenname: Leonardo A surname: Moraes fullname: Moraes, Leonardo A organization: NUS Immunology Program, Life Sciences Institute, NUS, Singapore, Singapore – sequence: 2 givenname: Shreya surname: Kar fullname: Kar, Shreya organization: Department of Pharmacology, Yong Loo Lin School of Medicine, NUS, Singapore, Singapore – sequence: 3 givenname: Sok Lin surname: Foo fullname: Foo, Sok Lin organization: NUS Graduate School for Integrative Sciences and Engineering, NUS, Singapore, Singapore – sequence: 4 givenname: Tong surname: Gu fullname: Gu, Tong organization: NUS Immunology Program, Life Sciences Institute, NUS, Singapore, Singapore – sequence: 5 givenname: Yi Qian surname: Toh fullname: Toh, Yi Qian organization: NUS Immunology Program, Life Sciences Institute, NUS, Singapore, Singapore – sequence: 6 givenname: Patrick B surname: Ampomah fullname: Ampomah, Patrick B organization: NUS Immunology Program, Life Sciences Institute, NUS, Singapore, Singapore – sequence: 7 givenname: Karishma surname: Sachaphibulkij fullname: Sachaphibulkij, Karishma organization: NUS Immunology Program, Life Sciences Institute, NUS, Singapore, Singapore – sequence: 8 givenname: Gracemary surname: Yap fullname: Yap, Gracemary organization: NUS Graduate School for Integrative Sciences and Engineering, NUS, Singapore, Singapore – sequence: 9 givenname: Olga surname: Zharkova fullname: Zharkova, Olga organization: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore – sequence: 10 givenname: Hakim M surname: Lukman fullname: Lukman, Hakim M organization: NUS Immunology Program, Life Sciences Institute, NUS, Singapore, Singapore – sequence: 11 givenname: Anna-Marie orcidid: 0000-0002-8950-6192 surname: Fairhurst fullname: Fairhurst, Anna-Marie organization: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore – sequence: 12 givenname: Alan Prem surname: Kumar fullname: Kumar, Alan Prem organization: Curtin Medical School, Faculty of Health Sciences, Curtin University, Perth, WA, Australia – sequence: 13 givenname: Lina H K surname: Lim fullname: Lim, Lina H K email: lina_lim@nuhs.edu.sg, lina_lim@nuhs.edu.sg, lina_lim@nuhs.edu.sg organization: NUS Graduate School for Integrative Sciences and Engineering, NUS, Singapore, Singapore. lina_lim@nuhs.edu.sg |
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Snippet | Macrophages are potent immune cells with well-established roles in the response to stress, injury, infection and inflammation. The classically activated... Abstract Macrophages are potent immune cells with well-established roles in the response to stress, injury, infection and inflammation. The classically... |
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SubjectTerms | Animals Annexin A1 - genetics Annexin A1 - metabolism Breast cancer Cell activation Cell Movement Cell Proliferation Extracellular Signal-Regulated MAP Kinases - metabolism Female Immunomodulation Inflammation Interleukin 4 Leukocyte migration Lipopolysaccharides Macrophages Macrophages - immunology Mammary Neoplasms, Animal - immunology Mammary Neoplasms, Animal - metabolism Mammary Neoplasms, Animal - pathology Metastases Mice Molecular modelling NF-kappa B - metabolism Polarization Receptors, Formyl Peptide - metabolism Signal Transduction Solid tumors Tumor Cells, Cultured Tumor microenvironment Tumor Microenvironment - immunology |
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Title | Annexin-A1 enhances breast cancer growth and migration by promoting alternative macrophage polarization in the tumour microenvironment |
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