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Expression of N-Acetylgalactosamine 4-Sulfate 6-O-Sulfotransferase Involved in Chondroitin Sulfate Synthesis Is Responsible for Pulmonary Metastasis

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Title: Expression of N-Acetylgalactosamine 4-Sulfate 6-O-Sulfotransferase Involved in Chondroitin Sulfate Synthesis Is Responsible for Pulmonary Metastasis
Authors: Mizumoto, Shuji Browse this author
Watanabe, Moto Browse this author
Yamada, Shuhei Browse this author
Sugahara, Kazuyuki Browse this author →KAKEN DB
Issue Date: 2013
Publisher: Hindawi Publishing Corporation
Journal Title: BioMed Research International
Volume: 2013
Start Page: 1
End Page: 9
Publisher DOI: 10.1155/2013/656319
PMID: 23555092
Abstract: Chondroitin sulfate (CS) containing E-disaccharide units, glucuronic acid-N-acetylgalactosamine(4, 6-O-disulfate), at surfaces of tumor cells plays a key role in tumor metastasis. However, the molecular mechanism of the metastasis involving the CS chaincontaining E-units is not fully understood. In this study, to clarify the role of E-units in the metastasis and to search for potential molecular targets for anticancer drugs, the isolation and characterization of Lewis lung carcinoma (LLC) cells stably downregulated by the knockdown for the gene encoding N-acetylgalactosamine 4-O-sulfate 6-O-sulfotransferase (GalNAc4S-6ST), which is responsible for the formation of E-units in CS chains, were performed. Knockdown of GalNAc4S-6ST in LLC cells resulted in a reduction in the proportion of E-units, in adhesiveness to extracellular matrix adhesion molecules and in proliferation in vitro. Furthermore, the stable downregulation of GalNAc4S-6ST expression in LLC cells markedly inhibited the colonization of the lungs by inoculated LLC cells and invasive capacity of LLC cells. ese results provide clear evidence that CS chain-containing E-units and/or GalNAc4S-6ST play a crucial role in pulmonary metastasis at least through the increased adhesion and the invasive capacity of LLC cells and also provides insights into future drug targets for anticancer treatment.
Rights: Copyright © 2013 Shuji Mizumoto et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
https://creativecommons.org/licenses/by/3.0/
Type: article
URI: http://hdl.handle.net/2115/62915
Appears in Collections:生命科学院・先端生命科学研究院 (Graduate School of Life Science / Faculty of Advanced Life Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 菅原 一幸

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