1. Pivotal Role for Cxcr2 in Regulating Tumor-Associated Neutrophil in Breast Cancer
- Author
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Timaxian, Colin, Vogel, Christoph FA, Orcel, Charlotte, Vetter, Diana, Durochat, Camille, Chinal, Clarisse, NGuyen, Phuong, Aknin, Marie-Laure, Mercier-Nomé, Françoise, Davy, Martin, Raymond-Letron, Isabelle, Van, Thi-Nhu-Ngoc, Diermeier, Sarah D, Godefroy, Anastasia, Gary-Bobo, Magali, Molina, Franck, Balabanian, Karl, and Lazennec, Gwendal
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Breast Cancer ,Aetiology ,2.1 Biological and endogenous factors ,chemokine receptors ,breast cancer ,Cxcr2 ,neutrophils ,tumor microenvironment ,Oncology and carcinogenesis - Abstract
Chemokines present in the tumor microenvironment are essential for the control of tumor progression. We show here that several ligands of the chemokine receptor Cxcr2 were up-regulated in the PyMT (polyoma middle T oncogene) model of breast cancer. Interestingly, the knock-down of Cxcr2 in PyMT animals led to an increased growth of the primary tumor and lung metastasis. The analysis of tumor content of PyMT-Cxcr2-/- animals highlighted an increased infiltration of tumor associated neutrophils (TANs), mirrored by a decreased recruitment of tumor associated macrophages (TAMs) compared to PyMT animals. Analysis of PyMT-Cxcr2-/- TANs revealed that they lost their killing ability compared to PyMT-Cxcr2+/+ TANs. The transcriptomic analysis of PyMT-Cxcr2-/- TANs showed that they had a more pronounced pro-tumor TAN2 profile compared to PyMT TANs. In particular, PyMT-Cxcr2-/- TANs displayed an up-regulation of the pathways involved in reactive oxygen species (ROS) production and angiogenesis and factors favoring metastasis, but reduced apoptosis. In summary, our data reveal that a lack of Cxcr2 provides TANs with pro-tumor effects.
- Published
- 2021