表面トポロジーによる癌細胞増殖抑制機構の解明

• Project/Area Number: 20670007
• Research Category: Grant-in-Aid for Young Scientists (S)
• Allocation Type: Single-year Grants
• Research Field: Biomedical engineering/Biological material science
• Research Institution: Yamagata University (2009-2011); Tohoku University (2008)
• Principal Investigator: 田中 賢 Yamagata University, 理工学研究科, 教授 (00322850)
• Project Period (FY): 2008 – 2012
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥83,330,000 (Direct Cost: ¥64,100,000、Indirect Cost: ¥19,230,000); Fiscal Year 2011: ¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000); Fiscal Year 2010: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000); Fiscal Year 2009: ¥20,800,000 (Direct Cost: ¥16,000,000、Indirect Cost: ¥4,800,000); Fiscal Year 2008: ¥29,250,000 (Direct Cost: ¥22,500,000、Indirect Cost: ¥6,750,000)
• Keywords: 自己組織化 / がん細胞 / 細胞増殖 / 表面 / バイオマテリアル / 医療・福祉 / 細胞接着 / 多孔質

Research Abstract

ナノ・マイクロパターン化表面上でがん細胞の増殖が低下するメカニズムおよび機能制御シグナルが長期間維持する仕組みの解明を行うために、電子線リソグラフィーによるトップダウン法ならびに自己組織化によるボトムアップ法の両方の手法により、様々な材質を用いてパターン化表面を作製した。パターン化表面上の細胞活性は、コントロール(ティッシュカルチャー:TC、フラットな表面:FF)と比べて低いことが分かった。TCおよびFF上で培養した細胞はトリプシン処理を行うと、すべて剥離するのに対し、パターン化表面上で培養した細胞は、基板に強固に接着しており剥離しなかった。剥離率はがん細胞の種類に依存した。発現タンパク質の解析から、トリプシン処理によるFFとパターン化表面からの剥離細胞では分裂を促進するタンパク質(Cyclin D1)が多く発現し、分裂を抑制するタンパク質(Rb)の発現は低かった。一方、トリプシン処理によりパターン化表面から剥離しなかった接着細胞ではCyclin D1が少なく、Rbが多いとことがわかった。電子顕微鏡観察より、トリプシン剥離前には細胞がパターン化表面に多く存在していたのに対し、剥離処理後にはパターン化表面の凹凸内部にのみ細胞が残っている様子が観察された。また、共焦点レーザ顕微鏡による断面観察から、パターン化表面の凹凸内部にまで潜り込み伸展している細胞が存在することがわかった。タンパク質発現の結果と顕微鏡観察の結果より、パターン化表面の凹凸内部に潜入し強く接着した細胞の増殖が抑制されている可能性があり、結果として細胞活性が抑制されているものと考えられる。以上の結果は、培養基材表面形状によりがん細胞の増殖が抑制される可能性を意味し、がん細胞増殖抑制機構の解明や体内治療デバイス開発など、がん治療に有用な基礎的な知見をもたらすものである。

Research Products

• [Journal Article] Design of Novel 2D and 3D Bio-Interfaces using Self-Organization to Control Cell behavior, Nanotechnologies : Emerging Applications in Biomedicine (2011)
  • Author(s): M.Tanaka
  • Journal Title: Biochimica et Biophysica Acta (BBA)-General Subjects Volume: 1810 Pages: 251-258
  • Peer Reviewed
• [Journal Article] Surface Segregation of Poly(2-methoxyethyl acrylate) in a Mixture with Poly(methyl methacrylate) (2011)
  • Author(s): M.Tanaka
  • Journal Title: Physical Chemistry Chemical Physics Volume: 13 Pages: 4928-4934
  • Peer Reviewed
• [Journal Article] Comparison of measurement techniques for the identification of bound water restrained by polymers (2011)
  • Author(s): M.Tanaka
  • Journal Title: Thermochim Acta Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Analyses of Water structures and dynamics of swollen blood compatible polymers (2011)
  • Author(s): M.Tanaka
  • Journal Title: Koubunshi Ronbunshu Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Design of Novel Bio-Interfaces using Self-Organization to Control Cell behavior (2011)
  • Author(s): M.Tanaka
  • Journal Title: Society for Medical and Biological Engineering Proceedings of the 49th Annual Conference of Japanese Society for Medical and Biological Engineering Volume: (CD-ROM)
• [Journal Article] バイオ界面における水分子の役割は?-次世代医療を切り開く生体親和性材料 (2011)
  • Author(s): M.Tanaka
  • Journal Title: 化学 Volume: 66 Pages: 68-69
• [Journal Article] Hot Topics, Water Structure of Biocompatible and Stimuli-Responsive Polymers with Alcoxy-alkyl Unit (2011)
  • Author(s): M.Tanaka
  • Journal Title: 高分子 Volume: 60 Pages: 3-4
• [Journal Article] Preface of special issue-Role of water molecules at the bio-interfaces at all hierachical (2011)
  • Author(s): M.Tanaka
  • Journal Title: Journal of Biomaterials Science : Polymer Edition Volume: 21 Pages: 1827-1829
• [Journal Article] 応用物理分野のアカデミック・ロードマップ バイオエレクトロニクス (2011)
  • Author(s): M.Tanaka
  • Journal Title: 応用物理 Volume: 79 Pages: 723-725
• [Journal Article] Clalification of blood compatibility mechanism by controlling water structure at the Blood-Poly(meth)acrylate Interface (2010)
  • Author(s): M.Tanaka
  • Journal Title: Journal of Biomaterials Science : Polymer Edition Volume: 21 Pages: 1849-1863
  • Peer Reviewed
• [Journal Article] Effect of Honeycomb-Patterned Surface Topography on the Function of Mesenteric Adipocytes (2010)
  • Author(s): M.Tanaka
  • Journal Title: Journal of Biomaterials Science : Polymer Edition Volume: 21 Pages: 1947-1956
  • Peer Reviewed
• [Journal Article] Hydration Structure of Poly(2-methoxyethyl acrylate) : comparison with a model monomer (2010)
  • Author(s): M.Tanaka
  • Journal Title: Journal of Biomaterials Science : Polymer Edition Volume: 21 Pages: 1925-1935
  • Peer Reviewed
• [Journal Article] 2H NMR and 13C NMR study of hydration behavior of poly(2-methoxyethyl acrylate)(PMEA), poly(2-hydroxyethyl methacrylate)(PHEMA) and poly(tetrahydrofurfuryl acrylate)(PTHFA) in relation to their blood compatibility as biomaterials (2010)
  • Author(s): M.Tanaka
  • Journal Title: Journal of Biomaterials Science : Polymer Edition Volume: 21 Pages: 1911-1924
• [Journal Article] Study on water structure and blood compatibility of poly(acryloylmorpholine-r-butyl methacrylate) (2010)
  • Author(s): M.Tanaka
  • Journal Title: Journal of Biomaterials Science : Polymer Edition Volume: 21 Pages: 1895-1910
  • Peer Reviewed
• [Journal Article] Thermal Properties of Freezing Bound Water Restrained by Polysaccharides (2010)
  • Author(s): M.Tanaka
  • Journal Title: Journal of Biomaterials Science : Polymer Edition Volume: 21 Pages: 1865-1880
  • Peer Reviewed
• [Journal Article] Mechanical effect of acetic acid lignin adsorption on honeycomb-patterned cellulosic films (2010)
  • Author(s): M.Tanaka
  • Journal Title: Journal of Wood Chemistry and Technology Volume: 30 Pages: 348-359
  • Peer Reviewed
• [Journal Article] Design of Novel 3D Bio-interfaces Using Self-Organization to Control Stem Cell Proliferation and Differentiation (2010)
  • Author(s): M.Tanaka
  • Journal Title: Special Proceeding Book of JST-CREST International Symposium Volume: 1 Pages: 71-78
• [Journal Article] Design of Novel 3D Bio-interfaces Using Self-Organization to Control Stem Cell Proliferation and Differentiation (2010)
  • Author(s): M.Tanaka
  • Journal Title: Special Proceeding Book of JST CREST International Symposium Volume: 1 Pages: 71-78
• [Journal Article] Network structures and dynamics of dry and swollen poly(acrylate)s.Characterization of high-and low-frequency motions as revealed by suppressed or recovered intensities(SRI)analysis of 13C NMR (2010)
  • Author(s): M.Tanaka
  • Journal Title: Polymer 50 Pages: 6091-6099
  • Peer Reviewed
• [Journal Article] Effect of Honeycomb-Patterned Surface Topography on the Function of Mesenteric Adipocytes (2010)
  • Author(s): M.Tanaka
  • Journal Title: Journal of Biomaterials Science : Polymer Edition (印刷中)
  • Peer Reviewed
• [Journal Article] Studies on bound water restrained by poly(2-methacr yloyloxyethyl phosphorylcholine)(PMPC) : Comparison of the polysaccharides-water systems (2010)
  • Author(s): M.Tanaka
  • Journal Title: Acta Biomaterialia 6 Pages: 2077-2082
  • Peer Reviewed
• [Journal Article] Proliferation of periodontal ligament cells on biodegradable honeycomb film scaffold with unified micropore organization, Journal of Biomechanical Science and Engineering (2010)
  • Author(s): M.Tanaka
  • Journal Title: Journal of Biomechanical Science and Engineering, Special Issue on Micro and Nanobiotechnology for Cells 5 Pages: 252-261
  • Peer Reviewed
• [Journal Article] Clarification of blood compatible mechanism by controlling water stucture (2010)
  • Author(s): M.Tanaka
  • Journal Title: Journal of Biomaterials Science : Polymer Edition (印刷中)
  • Peer Reviewed
• [Journal Article] Hydration Structure of Poly(2-Methoxyethyl Acrylate) : Comparison with a Model Monomer of 2-Methoxyethy 1 Acetate (2010)
  • Author(s): M.Tanaka
  • Journal Title: Journal of Biomaterials Science : Polymer Edition (印刷中)
  • Peer Reviewed
• [Journal Article] 2H NMR and 13C NMR study of hydration behavior of poly(2-methoxyethyl acrylate)(PMEA), poly(2-hydroxyethyl methacrylate)(PHEMA)and poly(tetrahydrofurfuryl acrylate)(PTHFA)in relation to their blood compatibility as biomaterials (2010)
  • Author(s): M.Tanaka
  • Journal Title: Journal of Biomaterials Science : Polymer Edition (印刷中)
  • Peer Reviewed
• [Journal Article] Study on water structure and blood compatibility of poly(acryloylmorpholine-r-butyl methacrylate) (2010)
  • Author(s): M.Tanaka
  • Journal Title: Journal of Biomaterials Science : Polymer Edition (印刷中)
  • Peer Reviewed
• [Journal Article] Thermal Properties of Freezing Bound Water Restrained by Polysaccharides (2010)
  • Author(s): M.Tanaka
  • Journal Title: Journal of Biomaterials Science : Polymer Edition (印刷中)
  • Peer Reviewed
• [Journal Article] Fabrication of ordered arrays of biodegradable polymer pincushions using self-organized honeycomb-patterned film (2009)
  • Author(s): M.Tanaka
  • Journal Title: Macromol Symp 279 Pages: 175-182
  • Peer Reviewed
• [Journal Article] Fabrication of Novel Biocompatible Surfaces by Two-photon Absorption with Femtosecond Laser (2009)
  • Author(s): M.Tanaka
  • Journal Title: Mol.Cryst.Liq.Cryst 505 Pages: 219-230
  • Peer Reviewed
• [Journal Article] Control of cell adhesion and functions using self-organized honeycomb patterned polymer films (2009)
  • Author(s): M.Tanaka
  • Journal Title: BIODEVICES 52 Pages: 390-393
  • Peer Reviewed
• [Journal Article] (2009)
  • Author(s): 田中賢, 下村政嗣
  • Journal Title: ソフトマター分子設計:キャラクタリゼーションから機能性材料まで,2章10,高分子のナノ・マイクロ加工(丸善) Pages: 114-124
• [Journal Article] ハニカムフィルムによる細胞機能制御 (2008)
  • Author(s): 田中賢
  • Journal Title: BIO INDUSTRY 25 Pages: 26-33
• [Presentation] Selective adhesion and proliferation of human Periodontal Ligament cells on poly(2-methoxyethyl acrylate) (2011)
  • Author(s): M.Tanaka
  • Organizer: Nanomedicine : Advanced Technologies for an Ageing Population
  • Place of Presentation: グラスゴー(英国)
  • Year and Date: 2011-03-23
• [Presentation] Selective adhesion behavior of endothelial cells on blood compatible polymers (2011)
  • Author(s): M.Tanaka
  • Organizer: Nanomedicine : Advanced Technologies for an Ageing Population
  • Place of Presentation: グラスゴー(英国)
  • Year and Date: 2011-03-23
• [Presentation] Design of Novel 2D and 3D Bio-lnterfaces using Self-Organization to Control Cell behavior (2011)
  • Author(s): M.Tanaka
  • Organizer: Nanomedicine : Advanced Technologies for an Ageing Population
  • Place of Presentation: グラスゴー(英国)(招待講演)
  • Year and Date: 2011-03-23
• [Presentation] ポリ(2-メトキシエチルアクリレート)表面における血管内皮細胞の選択的接着挙動 (2011)
  • Author(s): M.Tanaka
  • Organizer: 日本再生医療学会総会
  • Place of Presentation: 東京
  • Year and Date: 2011-03-01
• [Presentation] ポリ(2-メトキシエチルアクリレート)表面におけるヒト歯根膜細胞の選択的な接着と伸展 (2011)
  • Author(s): M.Tanaka
  • Organizer: 日本再生医療学会総会
  • Place of Presentation: 東京
  • Year and Date: 2011-03-01
• [Presentation] 血球細胞の非接着性と癌細胞の接着性を併せ持つ高分子表面の創製 (2011)
  • Author(s): M.Tanaka
  • Organizer: 日本再生医療学会総会
  • Place of Presentation: 東京
  • Year and Date: 2011-03-01
• [Presentation] 組織3次元構築を目指した組織工学 3次足場場材料による細胞機能制御 (2011)
  • Author(s): M.Tanaka
  • Organizer: 日本再生医療学会総会
  • Place of Presentation: 東京(招待講演)
  • Year and Date: 2011-03-01
• [Presentation] Design of Novel Bio-Interfaces using Self-Organization to Control Cell behavior (2010)
  • Author(s): M.Tanaka
  • Organizer: Transactions of the Materials Research Society of Japan
  • Place of Presentation: 横浜(招待講演)
  • Year and Date: 2010-12-22
• [Presentation] Design of Novel 2D and 3D Bio-Interfaces using Self-Organization to Control Stem Cell behavior (2010)
  • Author(s): M.Tanaka
  • Organizer: Regenerative Medicine & Stem Cell 2010
  • Place of Presentation: 上海(中国)(招待講演)
  • Year and Date: 2010-12-06
• [Presentation] 生体親和性材料が有する中間水構造 (2010)
  • Author(s): 田中賢
  • Organizer: 東京理科大学界面科学研究センターシンポジウム
  • Place of Presentation: 東京(招待講演)
  • Year and Date: 2010-11-27
• [Presentation] 優れた生体親和性を有するバイオ界面のデザイン (2010)
  • Author(s): 田中賢
  • Organizer: 新化学発展協会電子情報技術部会講演会
  • Place of Presentation: 東京(招待講演)
  • Year and Date: 2010-11-04
• [Presentation] Water Structure of Biocompatible and Stimuli-Responsive Polymers with Alcoxy-alkyl Unit (2010)
  • Author(s): 田中賢
  • Organizer: 高分子討論会
  • Place of Presentation: 札幌
  • Year and Date: 2010-09-15
• [Presentation] 次世代の医療技術を支える生体親和性材料の設計 (2010)
  • Author(s): 田中賢
  • Organizer: 山形大学工学部技術部職員研修
  • Place of Presentation: 山形(招待講演)
  • Year and Date: 2010-09-07
• [Presentation] 生体類似の水和構造を有する高分子バイオマテリアルの創製 (2010)
  • Author(s): 田中賢
  • Organizer: ソフトインターフェイスの分子科学ワークショップ「ソフト界面と水」
  • Place of Presentation: 福岡(招待講演)
  • Year and Date: 2010-08-11
• [Presentation] 再生医療が拓く未来 (2010)
  • Author(s): 田中賢
  • Organizer: 公開講座「健康と命を守るバイオ・医療技術の最前線
  • Place of Presentation: 山形(招待講演)
  • Year and Date: 2010-08-06
• [Presentation] Comparison of measurement techniques for the identification of bound water restrained by hydrophilic polymers (2010)
  • Author(s): 田中賢
  • Organizer: ICCT
  • Place of Presentation: 筑波
  • Year and Date: 2010-08-05
• [Presentation] 新規バイオマテリアルを用いた肥満細胞の制御 (2010)
  • Author(s): 田中賢
  • Organizer: 日本歯科心身医学会総会・学術大会
  • Place of Presentation: 広島
  • Year and Date: 2010-07-07
• [Presentation] デバイス技術による細胞解析・制御の最前線Design of Novel Bio-Interfaces using Self-Organization to Control Cell behavior (2010)
  • Author(s): 田中賢
  • Organizer: 日本生体医工学会大会
  • Place of Presentation: 大阪(招待講演)
  • Year and Date: 2010-06-25
• [Presentation] Design of novel 2D and 3D biocompatible interfaces for medical devices (2010)
  • Author(s): 田中賢
  • Organizer: The 6th International Symposium on Organic Molecular Electronics
  • Place of Presentation: 千葉(招待講演)
  • Year and Date: 2010-06-10
• [Presentation] Non-Biofouling能を有する合成ならびに生体高分子の水和構造 (2010)
  • Author(s): 田中賢
  • Organizer: 高分子学会年次大会
  • Place of Presentation: 横浜(招待講演)
  • Year and Date: 2010-05-26
• [Presentation] (ポリアクリル酸2-メトキシエチル/ポリメタクリル酸メチル)ブレンド膜表面の凝集構造 (2010)
  • Author(s): 田中賢
  • Organizer: 高分子学会年次大会
  • Place of Presentation: 横浜
  • Year and Date: 2010-05-26
• [Presentation] 生体親和性材料の設計 (2010)
  • Author(s): 田中賢
  • Organizer: JST新技術説明会
  • Place of Presentation: 東京(招待講演)
  • Year and Date: 2010-05-21
• [Presentation] 多孔性高分子膜を用いた細胞培養技術 (2009)
  • Author(s): 田中賢
  • Organizer: 東北テクノアーチ 特許技術ご紹介セミナー第1弾 医療・ライフサイエンス
  • Place of Presentation: 東京
  • Year and Date: 2009-12-02
• [Presentation] Control of cell behavior using self-organized 3-D honeycomb-patterned films (2009)
  • Author(s): 田中賢
  • Organizer: JSPS COLLOQUIUM-Frontiers in Nanobiotechnology from Engineering to Application for Cells- Albanova University Center
  • Place of Presentation: Royal Institute of Technology(KTH)
  • Year and Date: 2009-06-05
• [Presentation] 生体適合性材料の設計-水分子の構造・運動性制御による生体適合性の付与- (2009)
  • Author(s): 田中賢
  • Organizer: 高分子学会ポリマーフロンティア 先端医療を牽引する高分子材料
  • Place of Presentation: 東京
  • Year and Date: 2009-04-17
• [Presentation] 新規生体適合性高分子表面・界面の設計 (2009)
  • Author(s): 田中賢
  • Organizer: 2009高分子学会東北支部研究発表会
  • Place of Presentation: 弘前大学
• [Presentation] Control of Cell Fate Using Self-Organized Honeycomb-Patterned Films (2009)
  • Author(s): 田中賢
  • Organizer: Annual Conference of the Tissue and Cell Engineering Society
  • Place of Presentation: UKグラスブ
• [Presentation] Design of novel bio-interfaces using self-organization to control cell functions (2009)
  • Author(s): 田中賢
  • Organizer: International Symposium on Nanobio-Interfaces in Relation to Molecular Mobility
  • Place of Presentation: 東京
• [Presentation] Design of Novel Bio-Interfaces using Self-Organization to Control Cell behavior (2009)
  • Author(s): 田中賢
  • Organizer: Transactions of the Materials Research Society of Japan
  • Place of Presentation: 横浜
• [Presentation] CONTROL OF CELL ADHESION AND FUNCTIONS USING SELF-ORGANIZED HONEYCOMB-PATTERNED FILMS (2008)
  • Author(s): M. Tanaka
  • Organizer: IUMRS-ICA 2008
  • Place of Presentation: 名古屋
  • Year and Date: 2008-12-13
• [Presentation] 自己組織化によるナノ・マイクロパターン化材料の創製-細胞挙動を操るソフトマテリアルの設計- (2008)
  • Author(s): 田中賢
  • Organizer: 第67回癌学会学術会
  • Place of Presentation: つくば
  • Year and Date: 2008-11-27
• [Presentation] Novel bio-interfaces for tissue engineering (2008)
  • Author(s): M. Tanaka
  • Organizer: MPI Workshop
  • Place of Presentation: Stuttgart (Germany)
  • Year and Date: 2008-11-14
• [Presentation] ハニカム構造界面による細胞機能制御 (2008)
  • Author(s): 田中賢
  • Organizer: 北陸先端大マテリアルサイエンス特別講演会
  • Place of Presentation: 石川県
  • Year and Date: 2008-11-06
• [Presentation] Design and Fabrication of Novel Bio-interface using Self-organization to Control of Cell Functions (2008)
  • Author(s): M. Tanaka
  • Organizer: CRC International Symposium on Bio-interface and Biomass Conversion
  • Place of Presentation: 札幌
  • Year and Date: 2008-10-29
• [Presentation] Inhibitory effects of honeycomb films on the growth of human cancer cells (2008)
  • Author(s): J. Hamada
  • Organizer: 第67回癌学会学術会
  • Place of Presentation: 横浜
  • Year and Date: 2008-10-28
• [Presentation] 自己組織化ソフトマテリアルによる細胞機能制御 (2008)
  • Author(s): 田中賢
  • Organizer: 科学技術振興機構JSTイノベーションプラザ東海
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-22
• [Presentation] 自己組織化ハニカム構造高分子薄膜によるヒト癌細胞の増殖の抑制 (2008)
  • Author(s): 栃木隆
  • Organizer: 第57回高分子討論会
  • Place of Presentation: 大阪
  • Year and Date: 2008-09-25
• [Presentation] 自己組織化多孔質薄膜の孔径による細胞機能の制御 (2008)
  • Author(s): 田中賢
  • Organizer: 第57回高分子討論会
  • Place of Presentation: 大阪
  • Year and Date: 2008-09-24
• [Presentation] Control of cell adhesion and functions using self-organized honeycomb-patterned polymer films (2008)
  • Author(s): 田中賢
  • Organizer: 42nd World Polymer Congress
  • Place of Presentation: Taipei (Taiwan)
  • Year and Date: 2008-06-29
• [Presentation] 自己組織化ハニカム構造高分子薄膜によるヒト癌細胞の増殖と運動性の抑制 (2008)
  • Author(s): 栃木隆
  • Organizer: 第57回高分子学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2008-05-27
• [Book] バイオマテリアルの基礎 (2010)
  • Author(s): 田中賢
  • Total Pages: 258
  • Publisher: 日本医学館
• [Book] 多孔体の精密制御と機能・物性評価, 多孔質高分子薄膜 (2008)
  • Author(s): 田中賢
  • Publisher: ナイエンス&テクノロジー出版
• [Book] 次世代医療のための高分子材料工学, ハニカムフィルム界面 (2008)
  • Author(s): 田中賢
  • Publisher: シーエムシー出版