| Literature DB >> 30414170 |
Rie Kinoshita1, Hiroki Sato2, Akira Yamauchi3, Yuta Takahashi2, Yusuke Inoue4, I Wayan Sumardika1,5, Youyi Chen1, Nahoko Tomonobu1, Kota Araki2, Kazuhiko Shien2, Shuta Tomida6, Hidejiro Torigoe2, Kei Namba2, Eisuke Kurihara2, Yusuke Ogoshi2, Hitoshi Murata1, Ken-Ichi Yamamoto1, Junichiro Futami7, Endy Widya Putranto8, I Made Winarsa Ruma1,5, Hiromasa Yamamoto2, Junichi Soh2, Toshihiko Hibino9, Masahiro Nishibori10, Eisaku Kondo11, Shinichi Toyooka2, Masakiyo Sakaguchi1.
Abstract
The metastatic dissemination of cancer cells to remote areas of the body is the most problematic aspect in cancer patients. Among cancers, melanomas are notoriously difficult to treat due to their significantly high metastatic potential even during early stages. Hence, the establishment of advanced therapeutic approaches to regulate metastasis is required to overcome the melanoma disease. An accumulating mass of evidence has indicated a critical role of extracellular S100A8/A9 in melanoma distant metastasis. Lung S100A8/A9 is induced by melanoma cells from distant organs and it attracts these cells to its enriched lung environment since melanoma cells possess several receptors that sense the S100A8/A9 ligand. We hence aimed to develop a neutralizing antibody against S100A8/A9 that would efficiently block melanoma lung metastasis. Our protocol provided us with one prominent antibody, Ab45 that efficiently suppressed not only S100A8/A9-mediated melanoma mobility but also lung tropic melanoma metastasis in a mouse model. This prompted us to make chimeric Ab45, a chimera antibody consisting of mouse Ab45-Fab and human IgG2-Fc. Chimeric Ab45 also showed significant inhibition of the lung metastasis of melanoma. From these results, we have high hopes that the newly produced antibody will become a potential biological tool to block melanoma metastasis in future clinical settings.Entities:
Keywords: S100A8/A9; antibody; metastasis
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Year: 2018 PMID: 30414170 DOI: 10.1002/ijc.31982
Source DB: PubMed Journal: Int J Cancer ISSN: 0020-7136 Impact factor: 7.396