{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T13:25:53Z","timestamp":1788269153341,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T00:00:00Z","timestamp":1685404800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai","doi-asserted-by":"publisher","award":["23ZR1438600"],"award-info":[{"award-number":["23ZR1438600"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81972205"],"award-info":[{"award-number":["81972205"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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\u2010associated metastatic microenvironment contributes to the early metastatic colonisation of cancer cells in the lung.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>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).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Hepatocellular carcinoma cells reduce the secretion of histidine\u2010rich 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 FC\u03b3R1 on the neutrophil membrane while inhibiting PI3K and NF\u2010\u03baB activation, thereby reducing IL\u20108 secretion to reduce neutrophil recruitment. Meanwhile, HRG inhibited IL8\u2010MAPK and NF\u2010\u03baB pathway activation and ROS production, resulting in reduced NETs formation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.1283","type":"journal-article","created":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T02:22:44Z","timestamp":1685499764000},"source":"Crossref","is-referenced-by-count":53,"title":["HRG inhibits liver cancer lung metastasis by suppressing neutrophil extracellular trap formation"],"prefix":"10.1002","volume":"13","author":[{"given":"Yanze","family":"Yin","sequence":"first","affiliation":[{"name":"Department of Liver Surgery Renji Hospital School of Medicine Shanghai Jiao Tong University  Shanghai China"},{"name":"Shanghai Engineering Research Center of Transplantation and Immunology  Shanghai China"},{"name":"Shanghai Institute of Transplantation  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijuan","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of 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