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Title: | Cancer cells produce liver metastasis via gap formation in sinusoidal endothelial cells through proinflammatory paracrine mechanisms |
Author: | Hoang, Truong Huu Sato Matsubara, Misako Yuasa, Hideto Matsubara, Tsutomu Thuy, Le Thi Thanh Ikenaga, Hiroko Phuong, Dong Minh Hanh, Ngo Vinh Hieu, Vu Ngoc Hoang, Dinh Viet Hai, Hoang Okina, Yoshinori Enomoto, Masaru Tamori, Akihiro Daikoku, Atsuko Urushima, Hayato Ikeda, Kazuo Dat, Ninh Quoc Yasui, Yutaka Shinkawa, Hiroji Kubo, Shoji Yamagishi, Ryota Ohtani, Naoko Yoshizato, Katsutoshi Gracia Sancho, Jordi Kawada, Norufumi |
Keywords: | Càncer de fetge Endoteli Liver cancer Endothelium |
Issue Date: | 30-Sep-2022 |
Publisher: | American Association for the Advancement of Science (AAAS) |
Abstract: | Intracellular gap (iGap) formation in liver sinusoidal endothelial cells (LSECs) is caused by the destruction of fenestrae and appears under pathological conditions; nevertheless, their role in metastasis of cancer cells to the liver remained unexplored. We elucidated that hepatotoxin-damaged and fibrotic livers gave rise to LSECs-iGap formation, which was positively correlated with increased numbers of metastatic liver foci after intrasplenic injection of Hepa1-6 cells. Hepa1-6 cells induced interleukin-23-dependent tumor necrosis factor-α (TNF-α) secretion by LSECs and triggered LSECs-iGap formation, toward which their processes protruded to transmigrate into the liver parenchyma. TNF-α triggered depolymerization of F-actin and induced matrix metalloproteinase 9 (MMP9), intracellular adhesion molecule 1, and CXCL expression in LSECs. Blocking MMP9 activity by doxycycline or an MMP2/9 inhibitor eliminated LSECs-iGap formation and attenuated liver metastasis of Hepa1-6 cells. Overall, this study revealed that cancer cells induced LSEC-iGap formation via proinflammatory paracrine mechanisms and proposed MMP9 as a favorable target for blocking cancer cell metastasis to the liver. |
Note: | Reproducció del document publicat a: https://doi.org/10.1126/sciadv.abo5525 |
It is part of: | Science Advances, 2022, vol. 8, num. 39 |
URI: | http://hdl.handle.net/2445/209163 |
Related resource: | https://doi.org/10.1126/sciadv.abo5525 |
ISSN: | 2375-2548 |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) |
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