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Yansen Xiao, Min Cong, Jiatao Li, Dasa He, Qiuyao Wu, Pu Tian, Yuan Wang, Shuaixi Yang, Chenxi Liang, Yajun Liang and 17 more
Lung metastasis is the major cause of breast cancer-related mortality. The neutrophil-associated inflammatory microenvironment aids tumor cells in metastatic colonization in lungs. Here, we show that tumor-secreted protease cathepsin C (CTSC) promotes breast-to-lung metastasis by regulating recruitment of neutrophils and formation of neutrophil extracellular traps (NETs). CTSC enzymatically activates neutrophil membrane-bound proteinase 3 (PR3) to facilitate interleukin-1β (IL-1β) processing and nuclear factor κB activation, thus upregulating IL-6 and CCL3 for neutrophil recruitment. In addition, the CTSC-PR3-IL-1β axis induces neutrophil reactive oxygen species production and formation of NETs, which degrade thrombospondin-1 and support metastatic growth of cancer cells in the lungs. CTSC expression and secretion are associated with NET formation and lung metastasis in human breast tumors. Importantly, targeting CTSC with compound AZD7986 effectively suppresses lung metastasis of breast cancer in a mouse model. Overall, our findings reveal a mechanism of how tumor cells regulate neutrophils in metastatic niches and support CTSC-targeting approaches for cancer treatment.
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Xiao, Y., Cong, M., Li, J., He, D., Wu, Q., Tian, P., Wang, Y., Yang, S., Liang, C., Liang, Y., Wen, J., Liu, Y., Luo, W., Lv, X., He, Y., Cheng, D., Zhou, T., Zhao, W., Zhang, P., … Hu, G. (2021). Cathepsin C promotes breast cancer lung metastasis by modulating neutrophil infiltration and neutrophil extracellular trap formation. Cancer Cell, 39(3), 423–437.e7. https://doi.org/10.1016/j.ccell.2020.12.012
Xiao, Yansen, et al. "Cathepsin C promotes breast cancer lung metastasis by modulating neutrophil infiltration and neutrophil extracellular trap formation." Cancer Cell, vol. 39, no. 3, 2021, pp. 423–437.e7, https://doi.org/10.1016/j.ccell.2020.12.012.
Xiao, Yansen, Min Cong, Jiatao Li, Dasa He, Qiuyao Wu, Pu Tian, Yuan Wang, et al. "Cathepsin C promotes breast cancer lung metastasis by modulating neutrophil infiltration and neutrophil extracellular trap formation." Cancer Cell 39, no. 3 (2021): 423–437.e7. https://doi.org/10.1016/j.ccell.2020.12.012.
Xiao Y., Cong M., Li J. [и др.] Cathepsin C promotes breast cancer lung metastasis by modulating neutrophil infiltration and neutrophil extracellular trap formation // Cancer Cell. — 2021. — Vol. 39, № 3. — P. 423–437.e7. — URL: https://doi.org/10.1016/j.ccell.2020.12.012
@article{xiao2021cathepsin,
title = {{Cathepsin C promotes breast cancer lung metastasis by modulating neutrophil infiltration and neutrophil extracellular trap formation}},
author = {Yansen Xiao and Min Cong and Jiatao Li and Dasa He and Qiuyao Wu and Pu Tian and Yuan Wang and Shuaixi Yang and Chenxi Liang and Yajun Liang and Jili Wen and Yingjie Liu and Wenqian Luo and Xianzhe Lv and Yunfei He and Dongdong Cheng and Tianhao Zhou and Wenjing Zhao and Peiyuan Zhang and Xue Zhang and Yichuan Xiao and Youcun Qian and Hongxia Wang and Qiang Gao and Qingcheng Yang and Qifeng Yang and Guohong Hu},
journal = {Cancer Cell},
year = {2021},
volume = {39},
number = {3},
pages = {423--437.e7},
doi = {10.1016/j.ccell.2020.12.012},
url = {https://doi.org/10.1016/j.ccell.2020.12.012}
}TY - JOUR AU - Xiao, Yansen AU - Cong, Min AU - Li, Jiatao AU - He, Dasa AU - Wu, Qiuyao AU - Tian, Pu AU - Wang, Yuan AU - Yang, Shuaixi AU - Liang, Chenxi AU - Liang, Yajun AU - Wen, Jili AU - Liu, Yingjie AU - Luo, Wenqian AU - Lv, Xianzhe AU - He, Yunfei AU - Cheng, Dongdong AU - Zhou, Tianhao AU - Zhao, Wenjing AU - Zhang, Peiyuan AU - Zhang, Xue AU - Xiao, Yichuan AU - Qian, Youcun AU - Wang, Hongxia AU - Gao, Qiang AU - Yang, Qingcheng AU - Yang, Qifeng AU - Hu, Guohong TI - Cathepsin C promotes breast cancer lung metastasis by modulating neutrophil infiltration and neutrophil extracellular trap formation JO - Cancer Cell VL - 39 IS - 3 SP - 423 EP - 437.e7 PY - 2021 DA - 2021/01/14 DO - 10.1016/j.ccell.2020.12.012 UR - https://doi.org/10.1016/j.ccell.2020.12.012 ER -
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