TY - JOUR
T1 - IL-17–CXC Chemokine Receptor 2 Axis Facilitates Breast Cancer Progression by Up-Regulating Neutrophil Recruitment
AU - Wu, Lingyun
AU - Awaji, Mohammad
AU - Saxena, Sugandha
AU - Varney, Michelle L.
AU - Sharma, Bhawna
AU - Singh, Rakesh K.
N1 - Publisher Copyright:
© 2020 American Society for Investigative Pathology
PY - 2020/1
Y1 - 2020/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ajpath.2019.09.016
DO - 10.1016/j.ajpath.2019.09.016
M3 - Article
C2 - 31654638
AN - SCOPUS:85076249524
SN - 0002-9440
VL - 190
SP - 222
EP - 233
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 1
ER -