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National Institute of Environmental Health Sciences

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Publication Detail

Title: Pivotal Role for Cxcr2 in Regulating Tumor-Associated Neutrophil in Breast Cancer.

Authors: Timaxian, Colin; Vogel, Christoph F A; 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; Lazennec, Gwendal

Published In Cancers (Basel), (2021 May 25)

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.

PubMed ID: 34070438 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

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