IL-17–CXC Chemokine Receptor 2 Axis Facilitates Breast Cancer Progression by Up-Regulating Neutrophil Recruitment

Lingyun Wu, Mohammad Awaji, Sugandha Saxena, Michelle L. Varney, Bhawna Sharma, Rakesh K. Singh

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Recent evidence suggests that interactions among proinflammatory cytokines, chemokines, and cancer cell–recruited neutrophils result in enhanced metastasis and chemotherapy resistance. Nonetheless, the detailed mechanism remains unclear. Our aim was to discover the role of IL-17, CXC chemokine receptor 2 (CXCR2) ligands, and cancer-associated neutrophils in chemotherapy resistance and metastasis in breast cancer. Mice were injected with Cl66 murine mammary tumor cells, Cl66 cells resistant to doxorubicin (Cl66-Dox), or Cl66 cells resistant to paclitaxel (Cl66-Pac). Higher levels of IL-17 receptor, CXCR2 chemokines, and CXCR2 were observed in tumors generated from Cl66-Dox and Cl66-Pac cells in comparison with tumors generated from Cl66 cells. Tumors generated from Cl66-Dox and Cl66-Pac cells had higher infiltration of neutrophils and T helper 17 cells. In comparison with primary tumor sites, there were increased levels of CXCR2, CXCR2 ligands, and IL-17 receptor within the metastatic lesions. Moreover, IL-17 increased the expression of CXCR2 ligands and cell proliferation of Cl66 cells. The supernatant of Cl66-Dox and Cl66-Pac cells enhanced neutrophil chemotaxis. In addition, IL-17–induced neutrophil chemotaxis was dependent on CXCR2 signaling. Collectively, these data demonstrate that the IL-17–CXCR2 axis facilitates the recruitment of neutrophils to the tumor sites, thus allowing them to play a cancer-promoting role in cancer progression.

Original languageEnglish (US)
Pages (from-to)222-233
Number of pages12
JournalAmerican Journal of Pathology
Volume190
Issue number1
DOIs
StatePublished - Jan 2020

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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