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Molecular basis of the formation of blood vessels with different structures

Research Project

Project/Area Number 23590349
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General medical chemistry
Research InstitutionKanazawa Medical University

Principal Investigator

YONEKURA Hideto  金沢医科大学, 医学部, 教授 (80240373)

Co-Investigator(Kenkyū-buntansha) 池田 崇之  金沢医科大学, 医学部, 講師 (00374942)
吉冨 泰央  金沢医科大学, 医学部, 助教 (80399039)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords腫瘍血管新生 / 腫瘍転移 / 血管内皮細胞 / DNAミクロアレイ / ルイス肺がん細胞 / リンパ管内皮細胞 / 癌転移 / 血管微細構造 / ルイス肺癌細胞
Research Abstract

The aim of this study was to clarify the molecular basis of the formation of vessels with different structures. (1) LYVE1-positive endothelial cells (ECs) were detected in tumors of high metastatic Lewis lung carcinoma cells (H11), but not in low metastatic cell (P29) tumors. (2) DNA microarray analyses using RNAs isolated from tumor vessel ECs demonstrated that LYVE1 expression was up-regulated in ECs in H11 tumor whereas NRP1 expression was down-regulated. These results suggested that H11 cells can induce lymphatic-like vessels in their tumors. (3) Expression profile analyses of H11 and P29 cells identified 15 up-regulated and 10 down-regulated genes in H11 cells. (4) We selected genes that encode secretory proteins and constructed lentiviral vectors expressing shRNAs against the candidate genes. We then prepared tumor cells expressing the shRNAs, transplanted the cells to mice, and analyzed the formation of tumors and their vessels.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (36 results)

All 2014 2013 2012 2011 Other

All Journal Article (9 results) (of which Peer Reviewed: 9 results) Presentation (27 results) (of which Invited: 1 results)

  • [Journal Article] Osteocytic cell necrosis is caused by a combination of glucocorticoid-induced Dickkopf-1 and hypoxia2014

    • Author(s)
      Ueda S, Ichiseki T, Yoshitomi Y, Yonekura H, Ueda Y, Kaneuji A, Matsumoto T
    • Journal Title

      Med. Mol. Morphol

      Volume: (印刷中)[Epub ahead of print]

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Low-molecular weight fractions of Japanese soy sauce act as a RAGE antagonist via inhibition of RAGE trafficking to lipid rafts.2013

    • Author(s)
      Munesue S, Yamamoto Y, Urushihara R, Inomata K, Saito H, Motoyoshi S, Watanabe T, Yonekura H, Yamamoto H.
    • Journal Title

      Food Funct.

      Volume: 4(12) Issue: 12 Pages: 1835-1842

    • DOI

      10.1039/c2fo30359k

    • NAID

      120005373515

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Low molecular weight heparin suppresses receptor for advanced glycation end products-mediated expression of malignant phenotype in human fibrosarcoma cells.2013

    • Author(s)
      Takeuchi A, Yamamoto Y, Munesue S, Harashima A, Watanabe T, Yonekura H, Yamamoto H, Tsuchiya H.
    • Journal Title

      Cancer Sci.

      Volume: 104(6) Issue: 6 Pages: 740-749

    • DOI

      10.1111/cas.12133

    • NAID

      120005830605

    • Related Report
      2013 Annual Research Report 2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Loss of HITS (FAM107B) expression in cancers of multiple organs : tissue microarray analysis2012

    • Author(s)
      Nakajima H, Koizumi K, Tanaka T, Ishigaki Y, Yoshitake Y, Yonekura H, Sakuma T, Fukushima T, Umehara H, Ueno S, Minamoto T and Motoo Y
    • Journal Title

      International journal of oncology

      Volume: 41 Issue: 4 Pages: 1347-1357

    • DOI

      10.3892/ijo.2012.1550

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of a major enzyme for the synthesis and hydrolysis of cyclic ADP-ribose in amphibian cells and evolutional conservation of the enzyme from human to invertebrate2012

    • Author(s)
      Ikeda T, Takasawa S, Noguchi N, Nata K, Yamauchi A, Takahashi I, Yoshikawa T, Sugawara A, Yonekura H, Okamoto H.
    • Journal Title

      Mol Cell Biochem

      Volume: 366 Issue: 1-2 Pages: 69-80

    • DOI

      10.1007/s11010-012-1284-0

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Endogenous Secretory Receptor for Advanced Glycation End-Products Inhibits Amyloid-beta1-42 Uptake into Mouse Brain2012

    • Author(s)
      Sugihara T., Munesue S., Yamamoto Y., Sakurai S., Akhter N., Kitamura Y., Shiba K., Watanabe T., Yonekura H., Hayashi Y., Hamada J. I. and Yamamoto H.
    • Journal Title

      J Alzheimers Dis

      Volume: 28 Issue: 3 Pages: 709-720

    • DOI

      10.3233/jad-2011-110776

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Suppression of a neocortical potassium channel activity by intracellular amyloid-β and its rescue with Homer1a.2011

    • Author(s)
      Yamamoto K, Ueta Y, Wang L, Yamamoto R, Inoue N, Inokuchi K, Aiba A, Yonekura H, Kato N.
    • Journal Title

      Journal of Neuroscience

      Volume: 31 Issue: 31 Pages: 11100-11109

    • DOI

      10.1523/jneurosci.6752-10.2011

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of the COL2A1 Mutation in Patients with Type I Stickler Syndrome Using RNA from Freshly Isolated Peripheral White Blood Cells2011

    • Author(s)
      Yaguchi H, Ikeda T, Osada H, Yoshitake Y, Sasaki H, Yonekura H
    • Journal Title

      Genet. Test. Mol. Biomarkers

      Volume: 15(4) Issue: 4 Pages: 231-237

    • DOI

      10.1089/gtmb.2010.0138

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hypoxia down-regulates sFlt-1 (sVEGFR-1) expression in human microvascular endothelial cells by a mechanism involving mRNA alternative processing2011

    • Author(s)
      Ikeda T, Sun L, Tsuruoka N, Ishigaki Y, Yoshitomi Y, Yoshitake Y, Yonekura H
    • Journal Title

      Biochem. J

      Volume: 436(2) Issue: 2 Pages: 399-407

    • DOI

      10.1042/bj20101490

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 神経-血管相互作用を介した血管ネットワーク形成におけるJunBの機能2013

    • Author(s)
      吉冨泰央, 池田崇之, 吉竹佳の, 八田稔久, 加藤伸郎, 米倉秀人
    • Organizer
      金沢医科大学医学会第49回学術集会
    • Place of Presentation
      金沢医科大学(石川県内灘町)
    • Year and Date
      2013-07-06
    • Related Report
      2013 Final Research Report
  • [Presentation] 転移能の異なるルイス肺がん細胞株が形成する腫瘍中に誘導される血管の構造の差異の解明2013

    • Author(s)
      吉冨泰央, 池田崇之, 吉竹佳の, 岡山實, 小栗佳代子, 米倉秀人
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜パシフィコ(神奈川県横浜市)
    • Related Report
      2013 Final Research Report
  • [Presentation] 転移能の異なるルイス肺がん細胞株が形成する腫瘍中に誘導される血管の構造の差異の解明2013

    • Author(s)
      吉冨泰央, 池田崇之, 吉竹佳の, 岡山 實, 小栗佳代子, 米倉秀人
    • Organizer
      第86回 日本生化学会大会
    • Place of Presentation
      神奈川県横浜市 パシフィコ横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] 神経-血管相互作用を介した血管ネットワーク形成におけるJunBの機能2013

    • Author(s)
      吉冨泰央, 池田崇之, 吉竹佳の, 八田稔久, 加藤伸郎, 米倉秀人
    • Organizer
      金沢医科大学医学会 第49回学術集会
    • Place of Presentation
      石川県内灘町 金沢医科大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] 低酸素状態はmRNA選択的3'端プロセシングを介して微小血管内皮細胞の可溶型VEGF受容体(可溶型Flt-1)産生を抑制する2012

    • Author(s)
      池田崇之, 吉冨泰央,石垣靖人,吉竹佳の,米倉秀人
    • Organizer
      日本生化学会北陸支部第30回記念大会
    • Place of Presentation
      金沢歌劇座(石川県金沢)
    • Year and Date
      2012-05-26
    • Related Report
      2013 Final Research Report
  • [Presentation] 毛細血管内皮細胞のマトリゲル上での管腔形成過程ではEpac2の発現が上昇する2012

    • Author(s)
      吉竹佳の, 池田崇之, 吉冨泰央, 田中一美, 米倉秀人
    • Organizer
      第85回日本生化学会大会福岡
    • Place of Presentation
      福岡国際会議場, 福岡国際会議場, マリンメッセ福岡(福岡県福岡市)
    • Related Report
      2013 Final Research Report
  • [Presentation] Flt-1(VEGF受容体-1)mRNA選択的3'端プロセシング機構の解析2012

    • Author(s)
      池田崇之, 吉冨泰央, 吉竹佳の, 米倉秀人
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡国際会議場, マリンメッセ福岡(福岡県福岡市)
    • Related Report
      2013 Final Research Report
  • [Presentation] Increased expression of Epac2 during in vitro tube formation in human microvascular endothelial cells2012

    • Author(s)
      Yoshitake Y, Ikeda T, Yoshitomi Y, Yonekura H
    • Organizer
      22nd IUBMB & 37th FEBS Congress
    • Place of Presentation
      Sevilla, Spain
    • Related Report
      2013 Final Research Report
  • [Presentation] 血管内皮細胞における可溶型Flt-1(可溶型VEGF受容体-1)mRNA選択的3'端プロセシング機構の解析2012

    • Author(s)
      池田崇之, 吉冨泰央,石垣靖人,吉竹佳の,米倉秀人
    • Organizer
      第14回日本RNA学会年会
    • Place of Presentation
      東北大学100周年記念会館川内萩ホール(宮城県仙台市)
    • Related Report
      2013 Final Research Report
  • [Presentation] Ultraviolet B-induced expression of amphiregulin and growth differentiation factor 15 in human lens epithelial cells2012

    • Author(s)
      Osada H, Yoshitake Y, Ikeda T, Ishigaki Y, Takata T, Tomosugi N, Kubo E, Sasaki H, Yonekura H
    • Organizer
      International Conference on The Lens
    • Place of Presentation
      Hawaii, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] Increased expression of Epac2 during in vitro tube formation in human microvascular endothelial cells.2012

    • Author(s)
      Yoshitake Y
    • Organizer
      22nd IUBMB & 37th FEBS Congress
    • Place of Presentation
      Sevilla, Spain
    • Related Report
      2012 Research-status Report
  • [Presentation] 血管内皮細胞における可溶型Flt-1(可溶型VEGF受容体-1)mRNA選択的3’端プロセシング機構の解析.2012

    • Author(s)
      池田 崇之
    • Organizer
      第14回日本RNA学会年会
    • Place of Presentation
      仙台(東北大学100周年記念会館川内萩ホール)
    • Related Report
      2012 Research-status Report
  • [Presentation] Flt-1(VEGF受容体-1)mRNA選択的3’端プロセシング機構の解析.2012

    • Author(s)
      池田 崇之
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡(福岡国際会議場)
    • Related Report
      2012 Research-status Report
  • [Presentation] 毛細血管内皮細胞のマトリゲル上での管腔形成過程ではEpac2の発現が上昇する.2012

    • Author(s)
      吉竹 佳の
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡(福岡国際会議場)
    • Related Report
      2012 Research-status Report
  • [Presentation] 低酸素刺激による微小血管内皮細胞の可溶型VEGF受容体(可溶型Flt-1)産生の抑制2011

    • Author(s)
      池田崇之, 吉冨泰央, 石垣靖人, 吉竹佳の, 米倉秀人
    • Organizer
      RNAフロンティアミーティング2001
    • Place of Presentation
      あいち健康プラザ(愛知県大府市)
    • Year and Date
      2011-08-31
    • Related Report
      2013 Final Research Report
  • [Presentation] 低酸素刺激による微小血管内皮細胞の可溶型VEGF受容体(可溶型Flt-1)産生の抑制2011

    • Author(s)
      池田崇之, 吉冨泰央, 石垣靖人, 吉竹佳の, 米倉秀人
    • Organizer
      第83回日本生化学会北陸支部会
    • Place of Presentation
      金沢大学角間キャンパス(石川県金沢市)
    • Year and Date
      2011-05-28
    • Related Report
      2013 Final Research Report
  • [Presentation] Increased expression of Epac2 during in vitro tube formation in human microvascular endothekial cells2011

    • Author(s)
      吉竹佳の, 池田崇之, 吉冨泰央, 石垣靖人, 米倉秀人
    • Organizer
      第34回日本分子生物学会年会(The 34th Annual Meeting of the Molecular Biology Society of Japan)
    • Place of Presentation
      横浜パシフィコ(神奈川県横浜市)
    • Related Report
      2013 Final Research Report
  • [Presentation] 神経-血管相互作用により血管で活性化される遺伝子群の同定とその機能解析2011

    • Author(s)
      吉冨泰央, 池田崇之, 吉竹佳の, 加藤伸郎, 米倉秀人
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都国際会館(京都府京都市)
    • Related Report
      2013 Final Research Report
  • [Presentation] VEGFR-1 production is down-regulated under hypoxia in human microvascular endothelial cells by a mechanism involving alternative mRNA 3′-end processing2011

    • Author(s)
      Ikeda T, Yoshitomi Y, Ishigaki Y, Yoshitake Y, Yonekura H
    • Organizer
      日本分子生物学会第11回春季シンポジウム・金沢国際がん生物学シンポジウム
    • Place of Presentation
      石川県立音楽堂(石川県金沢市)
    • Related Report
      2013 Final Research Report
  • [Presentation] Hypoxia down-regulates sFlt-1 (sVEGFR-1) expression in human microvascular endothelial cells by a mechanism involving mRNA alternative processing.2011

    • Author(s)
      Ikeda T
    • Organizer
      36th FEBS Congress
    • Place of Presentation
      Torino, Italy
    • Related Report
      2011 Research-status Report
  • [Presentation] Ultraviolet B-induced expression of amphiregulin and growth differentiation factor 15 in human lens epithelial cells.2011

    • Author(s)
      Yoshitake Y
    • Organizer
      36th FEBS Congress
    • Place of Presentation
      Torino, Italy
    • Related Report
      2011 Research-status Report
  • [Presentation] 低酸素刺激による微小血管内皮細胞の可溶型VEGF受容体(可溶型Flt-1)産生の抑制.2011

    • Author(s)
      池田崇之
    • Organizer
      第83回日本生化学会北陸支部会
    • Place of Presentation
      金沢大学角間キャンパス(金沢市)
    • Related Report
      2011 Research-status Report
  • [Presentation] Soluble VEGFR-1 production is down-regulated under hypoxia in human microvascular endothelial cells by a mechanism involving alternative mRNA 3’-end processing.2011

    • Author(s)
      Ikeda T
    • Organizer
      日本分子生物学会第11回春季シンポジウム・金沢国際がん生物学シンポジウム
    • Place of Presentation
      石川県立音楽堂(金沢市)
    • Related Report
      2011 Research-status Report
  • [Presentation] 低酸素刺激による微小血管内皮細胞の可溶型VEGF受容体(可溶型Flt-1)産生の抑制.2011

    • Author(s)
      池田崇之
    • Organizer
      RNAフロンティアミーティング2001
    • Place of Presentation
      あいち健康プラザ(愛知県大府市)
    • Related Report
      2011 Research-status Report
  • [Presentation] 神経-血管相互作用により血管で活性化される遺伝子群の同定とその機能解析.2011

    • Author(s)
      吉冨泰央
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都国際会館(京都市)
    • Related Report
      2011 Research-status Report
  • [Presentation] Increased expression of Epac2 during in vitro tube formation in human microvascular endothelial cells.2011

    • Author(s)
      吉竹佳の
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜パシフィコ(横浜市)
    • Related Report
      2011 Research-status Report
  • [Presentation] 低酸素状態はmRNA選択的3’端プロセシングを介して微小血管内皮細胞の可溶型VEGF受容体(可溶型Flt-1)産生を抑制する.

    • Author(s)
      池田 崇之
    • Organizer
      日本生化学会北陸支部第30回記念大会
    • Place of Presentation
      金沢(金沢歌劇座)
    • Related Report
      2012 Research-status Report
    • Invited

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Published: 2011-08-05   Modified: 2019-07-29  

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