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癌遊走阻害のためのインテグリンを標的とした自己組織化ペプチドの設計
https://doi.org/10.15102/1394.00001397
https://doi.org/10.15102/1394.0000139709cec5c7-b13c-49e9-81cb-be249e439f0c
| 名前 / ファイル | ライセンス | アクション |
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Final Exam Abstract (42.9 kB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||
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| 公開日 | 2020-06-01 | |||||||
| タイトル | ||||||||
| タイトル | 癌遊走阻害のためのインテグリンを標的とした自己組織化ペプチドの設計 | |||||||
| 言語 | ja | |||||||
| タイトル | ||||||||
| タイトル | Design Integrin-targeted Molecular Self-assembling Peptides for Studying Cancer Migration Inhibition | |||||||
| 言語 | en | |||||||
| 言語 | ||||||||
| 言語 | eng | |||||||
| 資源タイプ | ||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||
| 資源タイプ | doctoral thesis | |||||||
| ID登録 | ||||||||
| ID登録 | 10.15102/1394.00001397 | |||||||
| ID登録タイプ | JaLC | |||||||
| アクセス権 | ||||||||
| アクセス権 | open access | |||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||
| 著者 (英) |
Roy, Sona Rani
× Roy, Sona Rani
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| 抄録 | ||||||||
| 内容記述タイプ | Other | |||||||
| 内容記述 | Cancer metastasis, the ability of cancer cell to change position within the tissue through migration and invasion represents the most deadly aspect of cancer. As one of the ongoing challenges in cancer therapy, it’s failed in most treatments. For example, cell surface receptor-integrin that functions as adhesion molecule is well-recognized drug target for anti-metastatic drug development. By targeting the integrin-ligand binding site, antibody, and small molecule antagonists have been commonly used. But these treatments only offer modest response rates on limited cancer types. Therefore, nanotechnology that has been widely applied in biomedical engineering is desired in the cancer metastasis treatment. Inspired by the facts that integrin density, clustering, and redistribution on cell surface are the key spatial features influencing cell motility, we intend to develop a molecular self-assembly (MSA) technology that suppresses cancer metastasis by regulating integrin spatial distribution. To achieve the goal, we designed and synthesized a library of self-assembling integrin ligands composed of 29 peptides made via conjugation of phenylalanine based hydrophobic peptide and various integrin ligands. After confirming that they self-assemble in aqueous solution, we examined these peptides in multiple cancer cell lines and screened out five peptides that exert caner-cell-specific migration. We further examined peptide 5 among the 5 peptides and observed the peptide shows inhibition on cancer invasion, spheroid growth and spreading. We explored the molecular mechanism of the peptide on migration inhibition and found the the self-assembly of the peptide forms nanostructured microdomain as nano-biointerface on cancer cell membrane. We examined the molecular consequences of the bio-nanointerface on mechanotransduction-related proteins, especially the Hippo signaling related ones. Finally, the peptide is applied in xenograft tumor models in mice to examine the efficacy of tumor suppression effect and the molecular consequences in vivo. The research work presented in the thesis is intend to establish an easy and practical strategy for anti-metastatic drug development, and illustrate how basic biochemical insights can be exploited as the basis for a nano-biointerface fabrication technology which links nanoscale protein activities to molecular biological activities to suppress metastasis. | |||||||
| 言語 | en | |||||||
| 口頭試問日 | ||||||||
| 値 | 2020-04-16 | |||||||
| 学位授与年月日 | ||||||||
| 学位授与年月日 | 2020-05-31 | |||||||
| 学位名 | ||||||||
| 学位名 | Doctor of Philosophy | |||||||
| 学位授与番号 | ||||||||
| 学位授与番号 | 甲第54号 | |||||||
| 学位授与機関 | ||||||||
| 学位授与機関識別子Scheme | kakenhi | |||||||
| 学位授与機関識別子 | 38005 | |||||||
| 学位授与機関名 | Okinawa Institute of Science and Technology Graduate University | |||||||
| 著者版フラグ | ||||||||
| 出版タイプ | VoR | |||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||
| 権利 | ||||||||
| 権利情報 | © 2020 The Author. | |||||||
