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HRG inhibits liver cancer lung metastasis by suppressing neutrophil extracellular trap formation

BACKGROUND: Distant metastasis is a sign of poor prognosis for cancer patients. Extrahepatic liver cancer metastases commonly spread to the lung. Remodelling of the metastatic microenvironment is essential for tumour metastasis. Neutrophil‐associated metastatic microenvironment contributes to the ea...

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Autores principales: Yin, Yanze, Dai, Huijuan, Sun, Xicheng, Xi, Zhifeng, Zhang, Jiang, Pan, Yixiao, Huang, Yongxin, Ma, Xueyun, Xia, Qiang, He, Kang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10230156/
https://www.ncbi.nlm.nih.gov/pubmed/37254661
http://dx.doi.org/10.1002/ctm2.1283
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author Yin, Yanze
Dai, Huijuan
Sun, Xicheng
Xi, Zhifeng
Zhang, Jiang
Pan, Yixiao
Huang, Yongxin
Ma, Xueyun
Xia, Qiang
He, Kang
author_facet Yin, Yanze
Dai, Huijuan
Sun, Xicheng
Xi, Zhifeng
Zhang, Jiang
Pan, Yixiao
Huang, Yongxin
Ma, Xueyun
Xia, Qiang
He, Kang
author_sort Yin, Yanze
collection PubMed
description BACKGROUND: Distant metastasis is a sign of poor prognosis for cancer patients. Extrahepatic liver cancer metastases commonly spread to the lung. Remodelling of the metastatic microenvironment is essential for tumour metastasis. Neutrophil‐associated metastatic microenvironment contributes to the early metastatic colonisation of cancer cells in the lung. METHOD: The lung metastasis models were constructed via treated cancer cells by tail vein injection into mice. And samples of lung were harvested at the indicated time to analyze tumor growth and immune cells in the microenvironment. Tumors and lung metastasis specimens were obtained via surgical operations for research purposes. Neutrophils were obtained from peripheral blood of patients with liver cancer or healthy donors (HD). RESULTS: Hepatocellular carcinoma cells reduce the secretion of histidine‐rich glycoprotein (HRG), regulate the recruitment and activation of neutrophils in the metastatic microenvironment and promote the production of neutrophil extracellular traps (NETs), thereby promoting liver cancer lung metastasis. HRG binds to FCγR1 on the neutrophil membrane while inhibiting PI3K and NF‐κB activation, thereby reducing IL‐8 secretion to reduce neutrophil recruitment. Meanwhile, HRG inhibited IL8‐MAPK and NF‐κB pathway activation and ROS production, resulting in reduced NETs formation. CONCLUSIONS: Our study reveals that liver cancer regulates neutrophil recruitment and NETs formation in the metastatic microenvironment by reducing HRG secretion, thereby promoting tumour lung metastasis. The results of this study will contribute to the development of possible strategies for treating metastases.
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spelling pubmed-102301562023-06-01 HRG inhibits liver cancer lung metastasis by suppressing neutrophil extracellular trap formation Yin, Yanze Dai, Huijuan Sun, Xicheng Xi, Zhifeng Zhang, Jiang Pan, Yixiao Huang, Yongxin Ma, Xueyun Xia, Qiang He, Kang Clin Transl Med Research Articles BACKGROUND: Distant metastasis is a sign of poor prognosis for cancer patients. Extrahepatic liver cancer metastases commonly spread to the lung. Remodelling of the metastatic microenvironment is essential for tumour metastasis. Neutrophil‐associated metastatic microenvironment contributes to the early metastatic colonisation of cancer cells in the lung. METHOD: The lung metastasis models were constructed via treated cancer cells by tail vein injection into mice. And samples of lung were harvested at the indicated time to analyze tumor growth and immune cells in the microenvironment. Tumors and lung metastasis specimens were obtained via surgical operations for research purposes. Neutrophils were obtained from peripheral blood of patients with liver cancer or healthy donors (HD). RESULTS: Hepatocellular carcinoma cells reduce the secretion of histidine‐rich glycoprotein (HRG), regulate the recruitment and activation of neutrophils in the metastatic microenvironment and promote the production of neutrophil extracellular traps (NETs), thereby promoting liver cancer lung metastasis. HRG binds to FCγR1 on the neutrophil membrane while inhibiting PI3K and NF‐κB activation, thereby reducing IL‐8 secretion to reduce neutrophil recruitment. Meanwhile, HRG inhibited IL8‐MAPK and NF‐κB pathway activation and ROS production, resulting in reduced NETs formation. CONCLUSIONS: Our study reveals that liver cancer regulates neutrophil recruitment and NETs formation in the metastatic microenvironment by reducing HRG secretion, thereby promoting tumour lung metastasis. The results of this study will contribute to the development of possible strategies for treating metastases. John Wiley and Sons Inc. 2023-05-30 /pmc/articles/PMC10230156/ /pubmed/37254661 http://dx.doi.org/10.1002/ctm2.1283 Text en © 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Yin, Yanze
Dai, Huijuan
Sun, Xicheng
Xi, Zhifeng
Zhang, Jiang
Pan, Yixiao
Huang, Yongxin
Ma, Xueyun
Xia, Qiang
He, Kang
HRG inhibits liver cancer lung metastasis by suppressing neutrophil extracellular trap formation
title HRG inhibits liver cancer lung metastasis by suppressing neutrophil extracellular trap formation
title_full HRG inhibits liver cancer lung metastasis by suppressing neutrophil extracellular trap formation
title_fullStr HRG inhibits liver cancer lung metastasis by suppressing neutrophil extracellular trap formation
title_full_unstemmed HRG inhibits liver cancer lung metastasis by suppressing neutrophil extracellular trap formation
title_short HRG inhibits liver cancer lung metastasis by suppressing neutrophil extracellular trap formation
title_sort hrg inhibits liver cancer lung metastasis by suppressing neutrophil extracellular trap formation
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10230156/
https://www.ncbi.nlm.nih.gov/pubmed/37254661
http://dx.doi.org/10.1002/ctm2.1283
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