Macrophages attenuate the transcription of CYP1A1 in breast tumor cells and enhance their proliferation

  • While aberrant cells are routinely recognized and removed by immune cells, tumors eventually escape innate immune responses. Infiltrating immune cells are even corrupted by the tumor to acquire a tumor-supporting phenotype. In line, tumor-associated macrophages are well-characterized to promote tumor progression and high levels of tumor-infiltrating macrophages are a poor prognostic marker in breast cancer. Here, we aimed to further decipher the influence of macrophages on breast tumor cells and determined global gene expression changes in three-dimensional tumor spheroids upon infiltration of macrophages. While various tumor-associated mRNAs were upregulated, expression of the cytochrome P450 family member CYP1A1 was markedly attenuated. Repression of CYP1A1 in tumor cells was elicited by a macrophage-shaped tumor microenvironment rather than by direct tumor cell-macrophage contacts. In line with changes in RNA expression profiles, macrophages enhanced proliferation of the tumor cells. Enhanced proliferation and macrophage presence further correlated with reduced CYP1A1 expression in patient tumors when compared with normal tissue. These findings are of interest in the context of combinatory therapeutic approaches involving cytotoxic and immune-modulatory compounds.
Author:Sofia Winslow, Anica Scholz, Peter Rappl, Thilo F. Brauß, Christina Mertens, Michaela JungORCiD, Andreas WeigertORCiDGND, Bernhard BrüneORCiD, Tobias SchmidORCiD
Pubmed Id:
Parent Title (English):PLoS one
Place of publication:Lawrence, Kan.
Contributor(s):Aamir Ahmad
Document Type:Article
Year of Completion:2019
Date of first Publication:2019/01/07
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/01/08
Tag:Breast cancer; Breast tumors; Gene expression; Immune cells; Macrophages; Messenger RNA; RNA extraction; RNA isolation
Issue:(1): e0209694
Page Number:12
First Page:1
Last Page:12
Copyright: © 2019 Winslow et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Institutes:Medizin / Medizin
Wissenschaftliche Zentren und koordinierte Programme / Sonderforschungsbereiche / Forschungskollegs
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0