TY - JOUR A1 - Winslow, Sofia A1 - Scholz, Anica A1 - Rappl, Peter A1 - Brauß, Thilo Felix A1 - Mertens, Christina A1 - Jung, Michaela A1 - Weigert, Andreas A1 - Brüne, Bernhard A1 - Schmid, Tobias T1 - Macrophages attenuate the transcription of CYP1A1 in breast tumor cells and enhance their proliferation T2 - PLoS one N2 - 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. KW - Breast tumors KW - Macrophages KW - Messenger RNA KW - Immune cells KW - Breast cancer KW - Gene expression KW - RNA extraction KW - RNA isolation Y1 - 2019 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/48580 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-485801 SN - 1932-6203 N1 - 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. VL - 14 IS - (1): e0209694 SP - 1 EP - 12 PB - PLoS CY - Lawrence, Kan. ER -