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

被引：27

作者：

Timaxian, Colin ^{[1
,2
]}

Vogel, Christoph F. A. ^{[3
]}

Orcel, Charlotte ^{[1
]}

Vetter, Diana ^{[1
]}

Durochat, Camille ^{[1
]}

Chinal, Clarisse ^{[1
]}

Nguyen, Phuong ^{[1
]}

Aknin, Marie-Laure ^{[4
]}

Mercier-Nome, Francoise ^{[4
]}

Davy, Martin ^{[1
]}

Raymond-Letron, Isabelle ^{[5
,6
]}

Van, Thi-Nhu-Ngoc ^{[1
]}

Diermeier, Sarah D. ^{[7
]}

Godefroy, Anastasia ^{[8
]}

Gary-Bobo, Magali ^{[8
]}

Molina, Franck ^{[1
]}

Balabanian, Karl ^{[2
,9
]}

Lazennec, Gwendal ^{[1
,2
]}

机构：

[1] CNRS, SYS2DIAG ALCEDIAG, 1682 Rue Valsiere, F-34184 Montpellier, France

[2] CNRS, GDR Microenvironm Tumor Niches 3697, Micronit, France

[3] Univ Calif Davis, Ctr Hlth & Environm, 1 Shields Ave, Davis, CA 95616 USA

[4] Univ Paris Saclay, CNRS, Inst Paris Saclay Innovat Therapeut, INSERM, F-92296 Chatenay Malabry, France

[5] Natl Vet Sch Toulouse, Dept Histopathol, F-31076 Toulouse, France

[6] CNRS, UMR UPS 5223, Platform Expt & Compared Histopathol, EFS,INSERM,U1031, F-31076 Toulouse, France

[7] Univ Otago, Dept Biochem, Dunedin 9016, New Zealand

[8] Univ Montpellier, CNRS, IBMM, ENSCM, F-34093 Montpellier, France

[9] Univ Paris, Inst Rech St Louis, EMiLy, INSERM,U1160, F-75010 Paris, France

来源：

CANCERS | 2021年 / 13卷 / 11期

关键词：

chemokine receptors; breast cancer; Cxcr2; neutrophils; tumor microenvironment; COLONY-STIMULATING FACTOR; SUPPRESSOR-CELLS; MAMMARY-TUMORS; BONE-MARROW; MOUSE MODEL; STEM-CELLS; EXPRESSION; GROWTH; ANGIOGENESIS; RECEPTOR;

D O I：

10.3390/cancers13112584

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Simple Summary Chemokines present in the tumor microenvironment are essential for the control of tumor progression. We show here that 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 and that they had a more pronounced pro-tumor TAN2 profile compared to PyMT TANs. 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. 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.

引用

页数：20

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