Characterization of endothelial side population cells in the tumor vasculature and their potential role for drug resistance.

• Project/Area Number: 25830080
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Osaka University
• Principal Investigator: NAITO Hisamichi 大阪大学, 微生物病研究所, 助教 (30570676)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 血管内皮幹細胞 / 腫瘍血管 / 血管新生 / 血管新生阻害剤 / Side population

Outline of Final Research Achievements

Angiogenesis is regarded as a hallmark in cancer development.In the previous work, we identified stem/progenitor like endothelial cell(EC) in the peripheral blood vessel. These endothelial stem-like cell possess EC colony-forming potential in vitro and contribute to angiogenesis by generating functional mature blood vessels in vivo. In this study, we characterized endothelial stem-like cells in the tumor vasculature and found that in the tumor vasclature, the percentage of stem-like cells were higher than normal tissues. We further examined contribution of these cells to the tumor vasculature by transplantation model and found that they produces numbers of ECs and contribute to the tumor blood vessels as functional vessels. Moreover, administration of anti-angiogenic drugs revealed their potential role for resistance to anti-angiogenic therapy.

Research Products

• [Journal Article] Evaluation of PSF1 as a prognostic biomarker for prostate cancer. (2015)
  • Author(s): Tahara H, Naito H, Kise K, Wakabayashi T, Kamoi K, Okihara K, Yanagisawa A, Nakai Y, Nonomura N, Morii E, Miki T, Takakura N
  • Journal Title: Prostate Cancer Prostatic Dis Volume: 18 Issue: 1 Pages: 56-62
  • DOI: 10.1038/pcan.2014.46
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Cell-sheet Therapy With Omentopexy Promotes Arteriogenesis and Improves Coronary Circulation Physiology in Failing Heart. (2015)
  • Author(s): Kainuma S, Miyagawa S, Fukushima S, Pearson J, Chen YC, Saito A, Harada A, Shiozaki M, Iseoka H, Watabe T, Watabe H, Horitsugi G, Ishibashi M, Ikeda H, Tsuchimochi H, Sonobe T, Fujii Y, Naito H, Umetani K, Shimizu T, Okano T, Kobayashi E, Daimon T, Ueno T, Kuratani T, Toda K, Takakura N, Hatazawa J, Shirai M, Sawa Y.
  • Journal Title: Mol Ther Volume: 23 Issue: 2 Pages: 374-386
  • DOI: 10.1038/mt.2014.225
  • Peer Reviewed
• [Journal Article] Identification of vascular endothelial side population cells in the choroidal vessels and their potential role in age-related macular degeneration. (2013)
  • Author(s): Wakabayashi T, Naito H, Takara K, Kidoya H, Sakimoto S, Oshima Y, Nishida K, Takakura N
  • Journal Title: Investigative Ophthalmology & Visual Science Volume: 54 Issue: 10 Pages: 6686-6693
  • DOI: 10.1167/iovs.13-12342
  • Peer Reviewed
• [Journal Article] Tumor endothelial cell-specific drug delivery system using apelin-conjugated liposomes. (2013)
  • Author(s): Kawahara H, Naito H, Takara K, Wakabayashi T, Kidoya H, Takakura N.
  • Journal Title: PLos One Volume: 8 Issue: 6 Pages: e65499-e65499
  • DOI: 10.1371/journal.pone.0065499
  • Peer Reviewed
• [Journal Article] An angiogenic role for adrenomedullin in choroidal neovascularization. (2013)
  • Author(s): Sakimoto S, Kidoya H, Kamei M, Naito H, Yamakawa D, Sakaguchi H, Wakabayashi T, Nishida K, Takakura N.
  • Journal Title: PLoS One Volume: 8 Issue: 3 Pages: e58096-e58096
  • DOI: 10.1371/journal.pone.0058096
  • Peer Reviewed
• [Journal Article] Critical role of Trib1 for the differentiation of adipose tissue-resident macrophages maintaining metabolic homeostasis. (2013)
  • Author(s): Satoh T, Kidoya H, Naito H, Yamamoto M, Takemura N, Nakagawa K, Yoshioka Y, Morii E, Takakura N, Takeuchi O, Akira S
  • Journal Title: Nature Volume: 495(7442) Issue: 7442 Pages: 524-528
  • DOI: 10.1038/nature11930
  • Peer Reviewed
• [Journal Article] Ligand-independent Tie2 dimers mediate kinase activity stimulated by high dose angiopoietin-1. (2013)
  • Author(s): Yamakawa D
  • Journal Title: J Biol Chem. Volume: 288 Issue: 18 Pages: 12469-12477
  • DOI: 10.1074/jbc.m112.433979
  • Peer Reviewed
• [Journal Article] Galectin-3 accelerates m2 macrophage infiltration and angiogenesis in tumors. (2013)
  • Author(s): Jia W
  • Journal Title: Am J Pathol. Volume: 182 Issue: 5 Pages: 1821-1831
  • DOI: 10.1016/j.ajpath.2013.01.017
  • Peer Reviewed
• [Journal Article] microRNA-125b inhibits tube formation of blood vessels through translational suppression of VE-cadherin (2012)
  • Author(s): Muramatsu F.
  • Journal Title: Oncogene Volume: (In press) Issue: 4 Pages: 414-421
  • DOI: 10.1038/onc.2012.68
  • Peer Reviewed
• [Presentation] Postnatal development of hierarchical system in vascular endothelial side population cells and its role in liver regeneration (2014)
  • Author(s): Taku Wakabayashi, Hisamichi Naito, Hiroyasu Kidoya, Nobuyuki Takakura
  • Organizer: Gordon Research Conference
  • Place of Presentation: Girona, Spain
  • Year and Date: 2014-07-06 – 2014-07-11
• [Presentation] Identification of a new endothelial cell population in the peripheral blood vessels (2014)
  • Author(s): Hisamichi Naito
  • Organizer: Gordon Research Conference
  • Place of Presentation: Girona, Spain
  • Year and Date: 2014-07-06 – 2014-07-11
• [Presentation] The investigation on possibility of existence of endothelial stem-like cell population in kidney (2014)
  • Author(s): Yamane Keitaro ,Wakabayashi Taku, Naito Hisamichi, Kidoya Hiroyasu, Takakura Nobuyuki
  • Organizer: 第12回幹細胞シンポジウム
  • Place of Presentation: 福岡
  • Year and Date: 2014-05-30 – 2014-05-31
• [Presentation] Identification of a new population of vascular resident endothelial cells (2014)
  • Author(s): Hisamichi Naito, Taku Wakabayashi, Kazuhiro Takara, Ryu Kanzaki, Hironori Yoshida, Kazuyoshi Kise, Fumitaka Muramatsu, Hiroyasu Kidoya, Nobuyuki Takakura
  • Organizer: The 18th International Vascular Biology Meeting.
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2014-04-14 – 2014-04-17
• [Presentation] 血管内皮幹細胞の同定と新規幹細胞マーカー解析 (2014)
  • Author(s): 内藤尚道、木戸屋浩康、若林卓、高倉伸幸
  • Organizer: 「iPS細胞」研究支援3制度合同シンポジウム2014
  • Place of Presentation: 東京
• [Presentation] Identification of Vascular Endothelial side Population and Its Role in Angiogenesis (2013)
  • Author(s): Hisamichi Naito and Nobuyuki Takakura
  • Organizer: 11th Japan-Korea Joint Symposium on Vascular Biology
  • Place of Presentation: Jeju, Korea
  • Invited
• [Presentation] 既存血管の内皮幹細胞と病態 (2013)
  • Author(s): 内藤尚道、若林卓、木戸屋浩康、高倉伸幸
  • Organizer: 第21回日本血管生物医学会学術総会
  • Place of Presentation: 大阪
  • Invited
• [Presentation] Postnatal development of hierarchical system in vascular endothelial cells and its role in liver regeneration (2013)
  • Author(s): Taku Wakabayashi, Hisamichi Naito, Kazuhiro Takara, Hiroyasu Kidoya, Nobuyuki Takakura
  • Organizer: 11th Japan-Korea Joint Symposium on Vascular Biology
  • Place of Presentation: Jeju, Korea
• [Presentation] Tumor vessel maturation by apelin/APJ system improves the efficiency of immunotherapy (2013)
  • Author(s): H. Kidoya, N. Kunii, H. Naito, C. Takeshita, N. Takakura
  • Organizer: The European Cancer Congress 2013
  • Place of Presentation: Amsterdam, Nederland
• [Presentation] microRNA-125b inhibits tumor angiogenesis through translational suppression of vascular endothelial cadherin (2013)
  • Author(s): 村松、木戸屋、内藤、高倉
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Book] Angiogenesis and Vascularisation (2013)
  • Author(s): Hisamichi Naito, Nobuyuki Takakura
  • Total Pages: 416
  • Publisher: Springer
• [Remarks] 大阪大学研究者総覧
  • URL: http://www.dma.jim.osaka-u.ac.jp/view?l=ja&u=6802
• [Remarks] 大阪大学研究者総覧
  • URL: http://www.dma.jim.osaka-u.ac.jp/view?l=ja&u=6802