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

by Durochat, Camille , Molina, Franck , Chinal, Clarisse , Godefroy, Anastasia , NGuyen, Phuong , Balabanian, Karl , Mercier-Nomé, Françoise , Raymond-Letron, Isabelle , Aknin, Marie-Laure , Timaxian, Colin , Van, Thi-Nhu-Ngoc , Vogel, Christoph F. A. , Davy, Martin , Lazennec, Gwendal , Vetter, Diana , Diermeier, Sarah D. , Orcel, Charlotte , Gary-Bobo, Magali

in Angiogenesis / Apoptosis / Biochemistry, Molecular Biology / Bone marrow / Breast cancer / Cancer / Chemokine receptors / Chemokines / Cloning / CXCR2 protein / Cytokines / Flow cytometry / Gene expression / Genomics / Infiltration / Inflammation / Leukocytes (neutrophilic) / Life Sciences / Ligands / Macrophages / Metastases / Metastasis / Neutrophils / Reactive oxygen species / Tumor microenvironment / Tumors

2021

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

2021

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

2021

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Journal Article

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

Durochat, Camille,

Molina, Franck,

Chinal, Clarisse,

Godefroy, Anastasia,

NGuyen, Phuong,

Balabanian, Karl,

Mercier-Nomé, Françoise,

Raymond-Letron, Isabelle,

Aknin, Marie-Laure,

Timaxian, Colin,

Van, Thi-Nhu-Ngoc,

Vogel, Christoph F. A.,

Davy, Martin,

Lazennec, Gwendal,

Vetter, Diana,

Diermeier, Sarah D.,

Orcel, Charlotte,

Gary-Bobo, Magali

2021

Overview

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.

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Publisher

MDPI AG,MDPI

Subject

Angiogenesis

/ Apoptosis

/ Biochemistry, Molecular Biology

/ Bone marrow

/ Breast cancer

/ Cancer

/ Chemokine receptors