Nidogen 1-Enriched Extracellular Vesicles Facilitate Extrahepatic Metastasis of Liver Cancer by Activating Pulmonary Fibroblasts to Secrete Tumor Necrosis Factor Receptor 1

Autor:	Herbert Pang, Man-Fung Yuen, Xiaowen Mao, Ernest Man Lok Kwong, William C. Cho, Sze Keong Tey, Yi Gao, Maria Pik Wong, Cherlie Lot Sum Yeung, Judy Wai Ping Yam, Victor W.S. Ma, Yi Man Eva Fung, Carmen Oi Ning Leung, Xiaoping Xu, James Chung-Man Ho, Lung-Yi Mak, Terence Kin Wah Lee, Peihua Cao, Clive Yik-Sham Chung, Danny Ka-Ho Wong
Rok vydání:	2020
Předmět:	Angiogenesis General Chemical Engineering General Physics and Astronomy Medicine (miscellaneous) 02 engineering and technology 010402 general chemistry 01 natural sciences Biochemistry Genetics and Molecular Biology (miscellaneous) Metastasis tumor necrosis factor receptor 1 medicine nidogen 1 General Materials Science Secretion lcsh:Science Lung Full Paper Cell growth business.industry General Engineering pre‐metastatic niche hepatocellular carcinoma respiratory system Full Papers 021001 nanoscience & nanotechnology medicine.disease digestive system diseases 0104 chemical sciences medicine.anatomical_structure Hepatocellular carcinoma Cancer research lcsh:Q Tumor necrosis factor receptor 1 0210 nano-technology Liver cancer business extracellular vesicles
Zdroj:	Advanced Science Advanced Science, Vol 7, Iss 21, Pp n/a-n/a (2020)
ISSN:	2198-3844
Popis:	In hepatocellular carcinoma (HCC) patients with extrahepatic metastasis, the lung is the most frequent site of metastasis. However, how the lung microenvironment favors disseminated cells remains unclear. Here, it is found that nidogen 1 (NID1) in metastatic HCC cell‐derived extracellular vesicles (EVs) promotes pre‐metastatic niche formation in the lung by enhancing angiogenesis and pulmonary endothelial permeability to facilitate colonization of tumor cells and extrahepatic metastasis. EV‐NID1 also activates fibroblasts, which secrete tumor necrosis factor receptor 1 (TNFR1), facilitate lung colonization of tumor cells, and augment HCC cell growth and motility. Administration of anti‐TNFR1 antibody effectively diminishes lung metastasis induced by the metastatic HCC cell‐derived EVs in mice. In the clinical perspective, analysis of serum EV‐NID1 and TNFR1 in HCC patients reveals their positive correlation and association with tumor stages suggesting the potential of these molecules as noninvasive biomarkers for the early detection of HCC. In conclusion, these results demonstrate the interplay of HCC EVs and activated fibroblasts in pre‐metastatic niche formation and how blockage of their functions inhibits distant metastasis to the lungs. This study offers promise for the new direction of HCC treatment by targeting oncogenic EV components and their mediated pathways. Nidogen 1‐enriched extracellular vesicle (EV‐NID1) activates pulmonary fibroblasts to secrete tumor necrosis factor receptor 1 (TNFR1) which favors lung metastasis of liver cancer. Serum EV‐NID1 and TNFR1 are potential noninvasive biomarkers for the early detection of liver cancer. This study also provides insights into a new direction of treatment by blocking the signals of EVs derived from tumor cells.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::908f4317b9c183bbfe19a68ed1c099a8 https://pubmed.ncbi.nlm.nih.gov/33173740 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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