Nidogen 1‐Enriched Extracellular Vesicles Facilitate Extrahepatic Metastasis of Liver Cancer by Activating Pulmonary Fibroblasts to Secrete Tumor Necrosis Factor Receptor 1. Issue 21 (19th August 2020)

• Record Type: Journal Article
• Authors: Mao, Xiaowen; Tey, Sze Keong; Yeung, Cherlie Lot Sum; Kwong, Ernest Man Lok; Fung, Yi Man Eva; Chung, Clive Yik Sham; Mak, Lung‐Yi; Wong, Danny Ka Ho; Yuen, Man‐Fung; Ho, James Chung Man; Pang, Herbert; Wong, Maria Pik; Leung, Carmen Oi‐Ning; Lee, Terence Kin Wah; Ma, Victor; Cho, William Chi‐Shing; Cao, Peihua; Xu, Xiaoping; Gao, Yi; Yam, Judy Wai Ping
• Is Part Of: Advanced science. Volume 7:Issue 21(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-08-19
• Subjects: extracellular vesicles -- hepatocellular carcinoma -- nidogen 1 -- pre‐metastatic niche -- tumor necrosis factor receptor 1; Science -- Periodicals; 505
• DOI: 10.1002/advs.202002157
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: 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. Abstract : 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.