Article ; Online: TAp73 represses NF-κB-mediated recruitment of tumor-associated macrophages in breast cancer.
Proceedings of the National Academy of Sciences of the United States of America
2021 Volume 118, Issue 10
Abstract: Infiltration of tumor-promoting immune cells is a strong driver of tumor progression. Especially the accumulation of macrophages in the tumor microenvironment is known to facilitate tumor growth and to correlate with poor prognosis in many tumor types. ... ...
| Abstract | Infiltration of tumor-promoting immune cells is a strong driver of tumor progression. Especially the accumulation of macrophages in the tumor microenvironment is known to facilitate tumor growth and to correlate with poor prognosis in many tumor types. TAp73, a member of the p53/p63/p73 family, acts as a tumor suppressor and has been shown to suppress tumor angiogenesis. However, what role TAp73 has in regulating immune cell infiltration is unknown. Here, we report that low levels of TAp73 correlate with an increased NF-κB-regulated inflammatory signature in breast cancer. Furthermore, we show that loss of TAp73 results in NF-κB hyperactivation and secretion of Ccl2, a known NF-κB target and chemoattractant for monocytes and macrophages. Importantly, TAp73-deficient tumors display an increased accumulation of protumoral macrophages that express the mannose receptor (CD206) and scavenger receptor A (CD204) compared to controls. The relevance of TAp73 expression in human breast carcinoma was further accentuated by revealing that TAp73 expression correlates negatively with the accumulation of protumoral CD163 |
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| MeSH term(s) | Animals ; Antigens, CD/immunology ; Antigens, Differentiation, Myelomonocytic/immunology ; Breast Neoplasms/immunology ; Breast Neoplasms/pathology ; Chemokine CCL2/immunology ; Female ; Humans ; Membrane Glycoproteins/immunology ; Mice ; NF-kappa B/immunology ; Receptors, Cell Surface/immunology ; Receptors, Immunologic/immunology ; Scavenger Receptors, Class A/immunology ; Signal Transduction/immunology ; Tumor Microenvironment/immunology ; Tumor Protein p73/immunology ; Tumor-Associated Macrophages/immunology ; Tumor-Associated Macrophages/pathology |
| Chemical Substances | Antigens, CD ; Antigens, Differentiation, Myelomonocytic ; CCL2 protein, human ; CD163 antigen ; Chemokine CCL2 ; MRC1 protein, human ; MSR1 protein, human ; Membrane Glycoproteins ; NF-kappa B ; Receptors, Cell Surface ; Receptors, Immunologic ; Scavenger Receptors, Class A ; Tumor Protein p73 |
| Language | English |
| Publishing date | 2021-02-26 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 209104-5 |
| ISSN | 1091-6490 ; 0027-8424 |
| ISSN (online) | 1091-6490 |
| ISSN | 0027-8424 |
| DOI | 10.1073/pnas.2017089118 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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