Targeting tumor metastasis by normalization of tumor blood vessels

2012 Fiscal Year Final Research Report

• Project/Area Number: 23659930
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Hokkaido University
• Principal Investigator: HIDA Kyoko 北海道大学, 大学院・歯学研究科, 特任准教授 (40399952)
• Co-Investigator(Kenkyū-buntansha): SHINDOH Masanobu 北海道大学, 大学院・歯学研究科, 教授 (20162802) ; HIDA Yasuhiro 北海道大学, 北海道大学病院, 講師 (30399919) ; OHGA Noritaka 北海道大学, 大学院・歯学研究科, 特任助教 (40548202)
• Project Period (FY): 2011 – 2012
• Keywords: 腫瘍血管 / がん / 転移

Research Abstract

We have isolated two different type of TECs (HM-TEC; isolated from highly metastatic tumor, and LM-TEC; isolated from low metastatic tumor) and found they are different in many aspects. Tumor cells were more attracted and adhesive to HM-TEC in vitro assay. They migrated through the HM-TEC monolayer most among all ECs. To address the question whether TECs contribute to tumor metastasis, low metastatic tumor cells were co-xenografted with each different type of EC (HM-TEC /LM-TEC/NEC) into nude mice. These results suggested that TECs in tumor microenvironment may activelyinduce tumor metastasis.

Research Products

• [Journal Article] 腫瘍血管内皮細胞の異常と癌の悪性化との関連 (2012)
  • Author(s): 樋田京子,大賀則孝,秋山廣輔,間石奈湖
  • Journal Title: 日本口腔腫瘍学会誌 Volume: 24(3) Pages: 88-94
  • Peer Reviewed
• [Journal Article] がん微小環境と腫瘍血管内皮細胞, "Drug Delivery System" (2012)
  • Author(s): 樋田京子
  • Journal Title: 特集「基礎から拓くDDS創薬フロンティア」日本DDS学会 Volume: 27(1) Pages: 34-39
  • Peer Reviewed
• [Journal Article] 腫瘍血管内皮細胞の異常性 (2012)
  • Author(s): 樋田京子
  • Journal Title: 「生化学」,社団法人日本生化学会 Volume: 84(1) Pages: 43-46
  • Peer Reviewed
• [Journal Article] Development of a novel DNA aptamerligand against primary cultured tumorendothelial cells (2012)
  • Author(s): Naznin Ara., et al.
  • Journal Title: PLoS ONE Volume: 7(12) Pages: e50174
  • Peer Reviewed
• [Journal Article] Size-controlled, dual-ligand modifiedliposomes that target the tumor vasculatureshow promise foruse in drug-resistantcancer therapy (2012)
  • Author(s): Takara K., et al.
  • Journal Title: J Controlled Release Volume: 162(1) Pages: 225-232
  • Peer Reviewed
• [Journal Article] Prostacyclin receptor in tumorendothelial cells promotes angiogenesis inan autocrine manner (2012)
  • Author(s): Osawa T., Ohga N., Hida Y ., Kitayama K.,Akiyama K., Onodera Y ., Fujie M.,Shinohara N., Nonomura K., Shindoh M., Hida K.
  • Journal Title: Cancer Sci Volume: 103(6) Pages: 1038-1044
  • Peer Reviewed
• [Journal Article] Tumor-derivedmicrovesicles induce proangiogenicphenotype in endothelial cells viaendocytosis (2012)
  • Author(s): Kawamoto T., Ohga N., Akiyama K., HirataN., Kitahara S, Maishi N., Osawa T.,Yamamoto K., Kondoh M., Shindoh M.,Hida Y., Hida K.
  • Journal Title: PLoS ONE Volume: 7(3) Pages: e34045
  • Peer Reviewed
• [Journal Article] Biglycan is a specific marker and anautocrine angiogenic factor of tumourendothelial cells (2012)
  • Author(s): Y amamoto K., Ohga N., Hida Y ., Maishi N.,Kawamoto T., Kitayama K., Akiyama K.,Osawa T., Kondoh M., Matsuda K.,Onodera Y ., Fujie M., Kaga K., Hirano S,Shinohara N., Shindoh M., Hida K.
  • Journal Title: Br J Cancer Volume: 106 Pages: 1214-1223
  • Peer Reviewed
• [Journal Article] CXCR7 : A novel tumorendothelial marker in renal cell carcinoma (2012)
  • Author(s): Maishi N., Ohga N., Hida Y ., Akiyama K.,Kitayama K., Osawa T., Onodera Y .,Shinohara N., Nonomura K., Shindoh M., Hida K.
  • Journal Title: Pathol Int Volume: 62(5) Pages: 309-317
  • DOI: DOI:10.1111/j.1440-1827.2012.02792.x
  • Peer Reviewed
• [Journal Article] Heterogeneity of Tumor Endothelial Cells: Comparisonbetween Tumor Endothelial Cells Isolatedfrom Highly Metastatic and LowMetastatic Tumors (2012)
  • Author(s): Ohga N., Ishikawa S., Maishi N., AkiyamaK., Hida Y ., Kawamoto T., Sadamoto Y .,Osawa T.,Y amamoto K., Kondoh M.,Ohmura H., Shinohara N., Nonomura K.,Shindoh M., Hida K.
  • Journal Title: Am J Pathol Volume: 180(3) Pages: 1294-1307
  • DOI: DOI:10.1016/j.ajpath.2011.11.035
  • Peer Reviewed
• [Journal Article] Tumorendothelial cells acquire drug resistance byMDR1 upregulation via VEGF signaling intumor microenvironment (2012)
  • Author(s): Akiyama K., Ohga N., Hida Y ., KawamotoT., Sadamoto Y ., Ishikawa S., Maishi N., Akino T., Kondoh M., Matsuda A., InoueN., Shindoh M. and Hida K.
  • Journal Title: Am J Pathol Volume: 180(3) Pages: 1283-1293
  • DOI: DOI:10.1016/j.ajpath.2011.11.029
  • Peer Reviewed
• [Journal Article] Altered angiogenesis in thetumor microenvironment (2011)
  • Author(s): Hida K., et al.
  • Journal Title: Pathol Int Volume: 61(11) Pages: 630-637
  • DOI: DOI:10.1111/j.1440-1827.2011.02726.x
  • Peer Reviewed
• [Journal Article] Dual-ligand modification of PEGylatedliposomes shows better cell selectivity andefficient gene delivery (2011)
  • Author(s): Kibria G ., et al.
  • Journal Title: J ControlledRelease Volume: 153(2) Pages: 141-148
  • DOI: doi:10.1016/j.jconrel.2011.03.012
  • Peer Reviewed
• [Journal Article] HuR keepsan angiogenic switch on by stabilizingRNA of VEGF and COX-2 in tumorendothelium (2011)
  • Author(s): Kurosu T., Ohga N., Hida Y., Maishi N.,Akiyama K., Kakuguchi W., Kuroshima T.,Kondo M., Akino T., Totsuka Y ., ShindohM., Higashino F. and Hida K.
  • Journal Title: Br J Cancer Volume: 104(5) Pages: 819-829
  • DOI: DOI:10.1038/bjc.2011.20
  • Peer Reviewed
• [Journal Article] Phenotype of tumor lymphatic vessels is aprognostic factor in human tonguesquamous cell carcinoma (2011)
  • Author(s): Nitta Y ., et al.
  • Journal Title: Oncol Lett Volume: 2(1) Pages: 79-83
  • DOI: DOI:10.3892/ol.2010.201
  • Peer Reviewed
• [Presentation] 低酸素環境における腫瘍血管ダイナミクス (2011)
  • Author(s): 樋田京子
  • Organizer: The 8thAnnual Meeting for theJapanese Association for Cancer andHypoxia Research
  • Place of Presentation: 北海道大学(札幌)
  • Year and Date: 20110129-0130
• [Presentation] 腫瘍血管の多様性とがんの転移 (2011)
  • Author(s): 樋田京子
  • Organizer: Recent Advance in TumorAngiogenesis 2011
  • Place of Presentation: グランドホテル浜松(浜松市)
  • Year and Date: 2011-12-03
• [Presentation] 腫瘍血管新生阻害療法における新たな局面 -Lesson from Basic research (2011)
  • Author(s): 樋田京子
  • Organizer: 函館 Basic Cancer Forum
  • Place of Presentation: ベルクラシック函館(函館市)
  • Year and Date: 2011-11-24
• [Presentation] がん細胞・組織の多様性の出現・維持に関わる微小環境因子」 ,"腫瘍血管内皮細胞の異常性がもたらすがん治療への影響 (2011)
  • Author(s): 樋田京子
  • Organizer: 平成23年度遺伝子病制御研究所共同研究集会
  • Place of Presentation: 北海道大学医学部フラテ会館(札幌市)
  • Year and Date: 2011-09-06
• [Presentation] 腫瘍血管特異性の解明と新たな血管新生阻害療法への応用 (2011)
  • Author(s): 樋田京子
  • Organizer: 大阪歯科大学大学院 50 周年記念講演会
  • Place of Presentation: 大阪歯科大学楠葉学舎(大阪府枚方市)
  • Year and Date: 2011-09-02
• [Presentation] A New Insights into Tumorendothelial cell (2011)
  • Author(s): Hida K.
  • Organizer: The 5thMeeting of AsianSociety of Oral and MaxillofacialPathology
  • Place of Presentation: 九州大学医学部百年講堂(Fukuoka, Japan)
  • Year and Date: 2011-08-24
• [Presentation] 血管の多様性～組織発生から疾患におけるダイナミクス」 , "Heterogeneity ofTumor Endothelium and Drug Resistance" (2011)
  • Author(s): 樋田京子
  • Organizer: 第63回日本細胞生物学会大会
  • Place of Presentation: 北海道大学クラーク会館、学術交流会館(札幌)
  • Year and Date: 2011-06-29
• [Presentation] NSCLCに対するアバスチンの治療戦略～, "腫瘍血管内皮細胞の特異性とその制御" (2011)
  • Author(s): 樋田京子
  • Organizer: ACCEL in Hokkaido
  • Place of Presentation: アートホテルズ札幌(札幌市)
  • Year and Date: 2011-06-18
• [Presentation] 腫瘍血管内皮細胞の多様な生物像 (2011)
  • Author(s): 樋田京子
  • Organizer: 第27回日本DDS学会学術集会
  • Place of Presentation: 東京大学本郷キャンパス(東京)
  • Year and Date: 2011-06-09
• [Presentation] がん組織における管の特異性の解明と新たな血管新生阻害療法への応用 (2011)
  • Author(s): 樋田京子
  • Organizer: 高知大学医学部歯科口腔外科学講座セミナー
  • Place of Presentation: 高知大学岡豊キャンパス(高知県南国市)
  • Year and Date: 2011-06-03
• [Presentation] 癌間質の異常,とくに腫瘍血管の特性と浸潤との関連性 (2011)
  • Author(s): 樋田京子
  • Organizer: 第100回日本病理学会総会コンパニオンミーティング4「口腔癌の浸潤:外科病理と分子病理の架け橋」
  • Place of Presentation: 東京大学(東京都)(震災のため中止,誌上発表)
  • Year and Date: 2011-05-01
• [Presentation] がん微小環境内における腫瘍-血管の相互作用 (2011)
  • Author(s): 樋田京子
  • Organizer: 第9回口腔医科学フロンティア学術集会
  • Place of Presentation: 九州大学(福岡市)
  • Year and Date: 2011-03-05
• [Book] V ascular mimicry (2011)
  • Author(s): 樋田京子
  • Total Pages: 206-207 頁
  • Publisher: 朝倉書店
• [Book] 腫瘍血管内皮細胞 (2011)
  • Author(s): 樋田京子
  • Total Pages: 208-209頁
  • Publisher: 朝倉書店
• [Remarks]
  • URL: http://www.den.hokudai.ac.jp/vascular-biology/
• [Patent(Industrial Property Rights)] トロポニン T と結合する DNA, これを用いた腫瘍組織における血管新生および/または脈管形成抑制剤ならびにこれを用いた細胞内へ目的物質が取り込まれることを促進する剤 (2012)
  • Inventor(s): アラナズニン, 兵藤守, 畠山浩人, 樋田京子, 大賀則孝, 原島秀吉
  • Industrial Property Rights Holder: アラナズニン, 兵藤守, 畠山浩人, 樋田京子, 大賀則孝, 原島秀吉
  • Industrial Property Number: 特許出願2012-124073
  • Filing Date: 2012-06-21
  • Overseas
• [Patent(Industrial Property Rights)] 腫瘍血管新生阻害剤 (2011)
  • Inventor(s): 樋田京子,樋田泰浩
  • Industrial Property Rights Holder: 北海道大学
  • Industrial Property Number: 特許出願PCT/JP2011/056639
  • Filing Date: 2011-03-18
  • Overseas
• [Patent(Industrial Property Rights)] 腫瘍血管新生阻害剤 (2011)
  • Inventor(s): 樋田京子,樋田泰浩
  • Industrial Property Rights Holder: 北海道大学
  • Industrial Property Number: 特許出願PCT/JP2011/056631
  • Filing Date: 2011-03-18
  • Overseas