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Article Dans Une Revue Cancers Année : 2021

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

Colin Timaxian
  • Fonction : Auteur
Christoph Vogel
  • Fonction : Auteur
Charlotte Orcel
  • Fonction : Auteur
Diana Vetter
  • Fonction : Auteur
Camille Durochat
  • Fonction : Auteur
Clarisse Chinal
  • Fonction : Auteur
Phuong Nguyen
  • Fonction : Auteur
Marie-Laure Aknin
  • Fonction : Auteur
Françoise Mercier-Nomé
  • Fonction : Auteur
Martin Davy
  • Fonction : Auteur
Isabelle Raymond-Letron
  • Fonction : Auteur
Thi-Nhu-Ngoc Van
Sarah Diermeier
Anastasia Godefroy
Magali Gary-Bobo
Karl Balabanian
Gwendal Lazennec

Résumé

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.

Dates et versions

hal-04310542 , version 1 (27-11-2023)

Identifiants

Citer

Colin Timaxian, Christoph Vogel, Charlotte Orcel, Diana Vetter, Camille Durochat, et al.. Pivotal Role for Cxcr2 in Regulating Tumor-Associated Neutrophil in Breast Cancer. Cancers, 2021, 13 (11), pp.2584. ⟨10.3390/cancers13112584⟩. ⟨hal-04310542⟩

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