Reference - Detail
| RRC ID | 78897 |
|---|---|
| Author | Huu Hoang T, Sato-Matsubara M, Yuasa H, Matsubara T, Thuy LTT, Ikenaga H, Phuong DM, Hanh NV, Hieu VN, Hoang DV, Hai H, Okina Y, Enomoto M, Tamori A, Daikoku A, Urushima H, Ikeda K, Dat NQ, Yasui Y, Shinkawa H, Kubo S, Yamagishi R, Ohtani N, Yoshizato K, Gracia-Sancho J, Kawada N. |
| Title | Cancer cells produce liver metastasis via gap formation in sinusoidal endothelial cells through proinflammatory paracrine mechanisms. |
| Journal | Sci Adv |
| 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. |
| Volume | 8(39) |
| Pages | eabo5525 |
| Published | 2022-9-30 |
| DOI | 10.1126/sciadv.abo5525 |
| PMID | 36170363 |
| PMC | PMC9519040 |
| MeSH | Actins / metabolism Animals Doxycycline / metabolism Endothelial Cells* / metabolism Humans Interleukin-23 / metabolism Liver / metabolism Liver Neoplasms* / pathology Matrix Metalloproteinase 2 / metabolism Matrix Metalloproteinase 9 / metabolism Mice Mice, Inbred Strains Tumor Necrosis Factor-alpha / metabolism |
| IF | 13.117 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 31 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | Colon-26(RCB2657) |