Nucleolin on the Cell Surface as a New Molecular Target for Gastric Cancer Treatment
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- Watanabe Tatsuro
- Research Institute for Clinical Oncology, Saitama Cancer Center Graduate School of Science and Engineering, Saitama University
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- Hirano Kazuya
- School of Pharmacy, Tokyo University of Pharmacy and Life Science
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- Takahashi Atsushi
- Research Institute for Clinical Oncology, Saitama Cancer Center Graduate School of Science and Engineering, Saitama University
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- Yamaguchi Kensei
- Hospital, Saitama Cancer Center
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- Beppu Masatoshi
- School of Pharmacy, Tokyo University of Pharmacy and Life Science
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- Fujiki Hirota
- Faculty of Pharmaceutical Sciences, Tokushima Bunri University
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- Suganuma Masami
- Research Institute for Clinical Oncology, Saitama Cancer Center
Bibliographic Information
- Other Title
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- Highlighted paper selected by editor-in-chief: Nucleolin on the cell surface as a new molecular target for gastric cancer treatment
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Abstract
Nucleolin is an abundant non-ribosomal protein found in nucleolus and a major component of silver-stained nucleolar organizer region (AgNOR), a histopathological marker of cancer which is highly elevated in cancer cells. We recently reported that nucleolin on the cell surface of mouse gastric cancer cells acts as a receptor for tumor necrosis factor-α-inducing protein (Tipα), a new carcinogenic factor of Helicobacter pylori. In this study, we first examined the localization of nucleolin on cell surface of five gastric cancer cell lines by cell fractionation and flow cytometry: We found that large amounts of nucleolin were present on surface of MKN-45, KATOIII, MKN-74, and AGS cells, with smaller amounts on surface of MKN-1 cells. The membrane fraction of normal epithelial cells of mouse glandular stomach did not contain much nucleolin, suggesting that translocation of nucleolin to the cell surface occurs during carcinogenesis, making for easier binding with Tipα. AS1411, a nucleolin targeted DNA aptamer, inhibited growth of gastric cancer cell lines in this order of potency: MKN-45>KATOIII>AGS>MKN-74=MKN-1, associated with induction of S-phase cell cycle arrest. Fluorescein isothiocyanate (FITC)-AS1411 was more rapidly incorporated into MKN-45 and AGS than into MKN-1 cells, based on varying amounts of cell surface nucleolin. We think that AS1411 first binds to nucleolin on the cell surface and that the binding complex is then incorporated into the cells. All results indicate that nucleolin on the cell surface is a new and promising therapeutic target for treatment of gastric cancer.
Journal
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- Biological and Pharmaceutical Bulletin
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Biological and Pharmaceutical Bulletin 33 (5), 796-803, 2010
The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390282679602450176
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- NII Article ID
- 130000248039
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- NII Book ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL BIB ID
- 10662141
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- CiNii Articles
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- Abstract License Flag
- Disallowed