このエントリーをはてなブックマークに追加
ID 63956
FullText URL
fulltext.pdf 1.94 MB
Author
Tomonobu, Nahoko Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kinoshita, Rie Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kaken ID researchmap
Wake, Hidenori Department of Pharmacology, Kindai University Faculty of Medicine ORCID Kaken ID publons researchmap
Inoue, Yusuke Faculty of Science and Technology, Division of Molecular Science, Gunma University
Ruma, I. Made Winarsa Faculty of Medicine, Udayana University
Suzawa, Ken Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences ORCID Kaken ID researchmap
Gohara, Yuma Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Komalasari, Ni Luh Gede Yoni Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Jiang, Fan Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Murata, Hitoshi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kaken ID publons researchmap
Yamamoto, Ken-Ichi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Sumardika, I. Wayan Faculty of Medicine, Udayana University
Chen, Youyi Department of General Surgery & Bio-Bank of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University
Futami, Junichiro Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University ORCID Kaken ID publons researchmap
Yamauchi, Akira Department of Biochemistry, Kawasaki Medical School
Kuribayashi, Futoshi Department of Biochemistry, Kawasaki Medical School
Kondo, Eisaku Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences
Toyooka, Shinichi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences ORCID Kaken ID publons researchmap
Nishibori, Masahiro Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kaken ID publons researchmap
Sakaguchi, Masakiyo Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences ORCID Kaken ID publons researchmap
Abstract
The dissection of the complex multistep process of metastasis exposes vulnerabilities that could be exploited to prevent metastasis. To search for possible factors that favor metastatic outgrowth, we have been focusing on secretory S100A8/A9. A heterodimer complex of the S100A8 and S100A9 proteins, S100A8/A9 functions as a strong chemoattractant, growth factor, and immune suppressor, both promoting the cancer milieu at the cancer-onset site and cultivating remote, premetastatic cancer sites. We previously reported that melanoma cells show lung-tropic metastasis owing to the abundant expression of S100A8/A9 in the lung. In the present study, we addressed the question of why melanoma cells are not metastasized into the brain at significant levels in mice despite the marked induction of S100A8/A9 in the brain. We discovered the presence of plasma histidine-rich glycoprotein (HRG), a brain-metastasis suppression factor against S100A8/A9. Using S100A8/A9 as an affinity ligand, we searched for and purified the binding plasma proteins of S100A8/A9 and identified HRG as the major protein on mass spectrometric analysis. HRG prevents the binding of S100A8/A9 to the B16-BL6 melanoma cell surface via the formation of the S100A8/A9 complex. HRG also inhibited the S100A8/A9-induced migration and invasion of A375 melanoma cells. When we knocked down HRG in mice bearing skin melanoma, metastasis to both the brain and lungs was significantly enhanced. The clinical examination of plasma S100A8/A9 and HRG levels showed that lung cancer patients with brain metastasis had higher S100A8/A9 and lower HRG levels than nonmetastatic patients. These results suggest that the plasma protein HRG strongly protects the brain and lungs from the threat of melanoma metastasis.
Keywords
S100A8/A9
HRG
metastasis
Published Date
2022-09-07
Publication Title
International Journal Of Molecular Sciences
Volume
volume23
Issue
issue18
Publisher
MDPI
Start Page
10300
ISSN
1422-0067
Content Type
Journal Article
language
English
OAI-PMH Set
岡山大学
Copyright Holders
© 2022 by the authors.
File Version
publisher
PubMed ID
DOI
Web of Science KeyUT
Related Url
isVersionOf https://doi.org/10.3390/ijms231810300
License
https://creativecommons.org/licenses/by/4.0/
Funder Name
Japan Society for the Promotion of Science
助成番号
20H03516