Premetastatic niche formation by circulating tumor endothelial cells

• Project/Area Number: 16K20554
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Hokkaido University
• Principal Investigator: Maishi Nako 北海道大学, 遺伝子病制御研究所, 助教 (00632423)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 腫瘍血管新生 / 腫瘍血管内皮細胞 / 転移

Outline of Final Research Achievements

It is reported the formation of supportive metastatic microenvironment, referred to as premetastatic niche, before arrival of metastatic cells. Tumor endothelial cells, lining tumor blood vessels, is known to circulate in blood. In this study, we investigated the role of TECs in tumor metastasis. TECs adhered lung tissues more compared to normal endothelial cells when they were injected into mice intravenously. We established skin transplantation model using GFP mouse. Tumor cells were injected under the skin graft, and then we detected GFP positive cells in the blood of the mouse. We will examine the mechanisms of tumor metastasis by circulating TECs which secrete many cytokines.

Research Products

• [Journal Article] Abnormalities of tumor endothelial cells and cancer progression (2018)
  • Author(s): Hida K., Maishi N.:
  • Journal Title: Oral Sci Int Volume: 15(1) Issue: 1 Pages: 1-6
  • DOI: 10.1016/s1348-8643(17)30041-1
  • NAID: 10031168583
  • Peer Reviewed / Open Access
• [Journal Article] ATP-binding cassette transporters in tumor endothelial cells and resistance to metronomic chemotherapy (2017)
  • Author(s): Hida K., Kikuchi H., Maishi N., Hida Y.
  • Journal Title: Cancer Lett Volume: 400 Pages: 305-310
  • Peer Reviewed
• [Journal Article] Tumor endothelial cells accelerate tumor metastasis (2017)
  • Author(s): Maishi Nako、Hida Kyoko
  • Journal Title: Cancer Sci Volume: 108 Issue: 10 Pages: 1921-1926
  • DOI: 10.1111/cas.13336
  • Peer Reviewed
• [Journal Article] 腫瘍微小環境における血管系の異常 (2017)
  • Author(s): 樋田京子，間石奈湖
  • Journal Title: 医学書院 生体の科学 特集 血管制御系と疾患 Volume: 68(4) Pages: 321-323
• [Journal Article] Aneuploidy of murine immortalized endothelial cell line, MS1. (2017)
  • Author(s): Hida K., Maishi N., Dorcas Akuba-Muhyia Annan, Kondoh M., Hojo T., Umma Habiba, Ohga N., Ishikawa K, Sato M., Torii C., Yanagiya M., Morimoto M., Hida Y., Shindoh M.
  • Journal Title: J Oral Biosci Volume: 59 Issue: 1 Pages: 50-54
  • DOI: 10.1016/j.job.2016.10.004
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Vasohibin-1 as a novel prognostic factor for head and neck squamous cell carcinoma (2017)
  • Author(s): Torii C., Hida Y., Shindoh M., Akiyama K., Ohga N., Maishi N., Ohiro Y., Ono M., Totsuka Y., Kitagawa Y., Tei K., Sato Y., *Hida K
  • Journal Title: Anticancer Res Volume: 37(3) Pages: 1219-1225
  • Peer Reviewed
• [Journal Article] ROS enhance angiogenic properties via regulation of NRF2 in tumor endothelial cells (2017)
  • Author(s): Hojo Takayuki、Maishi Nako、Towfik Alam Mohammad、Akiyama Kosuke、Ohga Noritaka、Shindoh Masanobu、Hida Yasuhiro、Minowa Kazuyuki、Fujisawa Toshiaki、Hida Kyoko
  • Journal Title: Oncotarget Volume: 8 Issue: 28 Pages: 45484-45495
  • DOI: 10.18632/oncotarget.17567
  • NAID: 120006344445
  • Peer Reviewed / Open Access
• [Journal Article] miR-145 Promoted Anoikis Resistance in Tumor Endothelial Cells. (2017)
  • Author(s): 8.Hida K, Kawamoto T, Maishi N, Morimoto M, Akiyama K, Ohga N, Shindoh M, Shinohara N, Hida Y
  • Journal Title: Journal of biochemistry Volume: 162 Issue: 2 Pages: 81-84
  • DOI: 10.1093/jb/mvx033
  • NAID: 40021299734
  • Peer Reviewed / Open Access
• [Journal Article] Tumor Endothelial Cells with High Aldehyde Dehydrogenase Activity Show drug resistance (2017)
  • Author(s): 9.Hida K, Maishi N, Akiyama K, Ohmura-Kakutani H, Torii C, Ohga N, Osawa T, Kikuchi H, Morimoto H, Morimoto M et al
  • Journal Title: Cancer Sci Volume: 108 Issue: 11 Pages: 2195-2203
  • DOI: 10.1111/cas.13388
  • NAID: 120006373733
  • Peer Reviewed / Open Access
• [Journal Article] 腫瘍血管・腫瘍血管内皮細胞の特徴とその分子機構 (2016)
  • Author(s): 間石奈湖，樋田京子
  • Journal Title: 医学のあゆみ Volume: 258(1) Pages: 11-14
• [Journal Article] Tumor angiogenesis-characteristics of tumor endothelial cells. (2016)
  • Author(s): Hida K, Maishi N, Torii C, Hida Y.
  • Journal Title: Int J Clin Oncol Volume: 21 Issue: 2 Pages: 206-212
  • DOI: 10.1007/s10147-016-0957-1
  • Peer Reviewed
• [Journal Article] Heterogeneity of tumor endothelial cells and drug delivery (2016)
  • Author(s): Hida K, Maishi N, Sakurai Y, Hida Y, Harashima H
  • Journal Title: Adv Drug Deliv Rev Volume: 99 Pages: 140-147
  • DOI: 10.1016/j.addr.2015.11.008
  • Peer Reviewed
• [Journal Article] Tumor endothelial cells express high pentraxin 3 levels (2016)
  • Author(s): Hida K., Maishi N., Kawamoto T., Akiyama K., Ohga N., Hida Y., Yamada K., Hojo T., Kikuchi H., Sato M., Torii C., Shinohara N., Shindoh M
  • Journal Title: Pathol Int Volume: 66 Issue: 12 Pages: 687-694
  • DOI: 10.1111/pin.12474
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of characteristics of mouse immortalized normal endothelial cells, MS1 and primary cultured endothelial cells. (2016)
  • Author(s): Hida K., Maishi N., Torii C., Yanagiya M., Annan Akuba-Muhyia Dorcas., Morimoto M., Alam Mohammad Towfik
  • Journal Title: Hokkaido J. Dent. Sci. Volume: 37 Pages: 40-48
  • NAID: 120005855959
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan. (2016)
  • Author(s): N. Maishi, Y. Ohba, K. Akiyama, N. Ohga, J.I. Hamada, H. Nagao-Kitamoto, M. Alam, K. Yamamoto, T. Kawamoto, N. Inoue, A. Taketomi, M. Shindoh, Y. Hida and K. Hida.
  • Journal Title: Sci. Rep. Volume: 6 Issue: 1 Pages: 28039-28039
  • DOI: 10.1038/srep28039
  • NAID: 120005819304
  • Peer Reviewed / Open Access
• [Presentation] 腫瘍血管内皮細胞によるBiglycanの分泌を介したがんの転移促進 (2017)
  • Author(s): 間石奈湖
  • Organizer: 第２回口腔医科学フロンティア研究会
  • Place of Presentation: ZAOセンタープラザ（山形市）
  • Year and Date: 2017-03-05
• [Presentation] 肺癌症例における腫瘍血管内皮マーカーbiglycanの発現解析 (2017)
  • Author(s): 森本浩史，間石奈湖，樋田泰浩，西原広史，畑中 豊，松野吉宏，平野 聡，樋田京子
  • Organizer: 第116回北海道癌談話会例会
• [Presentation] Glutamine Metabolism in Tumor Endothelial Cells (2017)
  • Author(s): Dorcas A.Annan, 間石奈湖，曽我朋義，Dawood Randa, 樋田泰浩，樋田京子
  • Organizer: 第116回北海道癌談話会例会
• [Presentation] Glutamine Metabolism in Tumor Endothelial Cells (2017)
  • Author(s): Dorcas A. Annan, Maishi N., Soga T., Randa Dawood, Hida Y., Hida K.
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] Analysis of multidrug resistant transporter expression in tumor blood vessels during chemotherapy (2017)
  • Author(s): 間石奈湖，菊地 央，森本浩史，土屋邦彦，安部崇重，樋田泰浩，原林 透，松野吉宏，篠原信雄，樋田京子
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] 肺癌症例における腫瘍血管内皮細胞マーカーbiglycanの発現解析 (2017)
  • Author(s): 森本浩史，間石奈湖，樋田泰浩，西原広史，畑中 豊，松野吉宏，中村 透，平野 聡，樋田京子
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] 高転移性腫瘍由来エクソソームmiRNAによる血管内皮の薬剤耐性誘導 (2017)
  • Author(s): 森本真弘, 間石奈湖, 樋田京子
  • Organizer: 第59回歯科基礎医学会学術大会
• [Presentation] 抗癌剤治療による腫瘍血管内皮細胞の薬剤耐性獲得機構 (2017)
  • Author(s): 武田 遼，森本真弘，間石奈湖，樋田京子
  • Organizer: 第59回歯科基礎医学会学術大会
• [Presentation] Tumor endothelial cells in high metastatic tumors promote metastasis via biglycan (2017)
  • Author(s): Maishi N., Hida K.
  • Organizer: Protein Island Matsuyama 2017
  • Int'l Joint Research / Invited
• [Presentation] 高転移性腫瘍miRによる血管内皮における薬剤耐性誘導 (2017)
  • Author(s): 間石奈湖, 鳥居ちさほ, 川本泰輔, 森本真弘, 秋山廣輔, 吉岡祐亮, Alam Mohammad Towfik, 南 敬, 落谷孝広, 樋田泰浩, 樋田京子
  • Organizer: 第26回日本がん転移学会学術集会
• [Presentation] 尿路上皮癌における抗癌剤治療後の腫瘍血管ABCB1発現亢進 (2017)
  • Author(s): 菊地 央, 間石奈湖, 秋山廣輔, 森本真弘, 土屋邦彦, 丸山 覚, 安部崇重, 樋田 泰浩, 原林 透, 飴田 要, 松本隆児, 柏木 明, 松野吉宏, 篠原信雄, 樋田京子
  • Organizer: 第26回日本がん転移学会学術集会
• [Presentation] 肺癌症例における腫瘍血管内皮マーカーbiglycanの発現解析 (2017)
  • Author(s): 森本浩史, 間石奈湖, 樋田泰浩, 西原広史, 畑中 豊, 松野吉宏, 中村 透, 平野 聡, 樋田京子
  • Organizer: 第26回日本がん転移学会学術集会
• [Presentation] P-glycoprotein expression dynamics in tumor blood vessels of urothelial carcinoma during chemotherapy (2016)
  • Author(s): 菊地 央，間石奈湖，秋山廣輔，森本真弘，柳谷美沙，土屋邦彦，安部崇重，樋田泰浩，原林 透，飴田 要，柏木 明，田中伸哉，松野吉宏，篠原信雄，樋田京子
  • Organizer: 第24回日本血管生物医学会学術集会
  • Place of Presentation: 長崎ブリックホール（長崎市）
  • Year and Date: 2016-12-10
• [Presentation] Correlation between CXCR7 expression of blood vessels and clinicopathological features in oral squamous cell carcinoma (2016)
  • Author(s): 柳谷美沙，間石奈湖，鳥居ちさほ，樋田泰浩，大賀則孝，鄭 漢忠，進藤正信，北川善政，樋田京子
  • Organizer: 第24回日本血管生物医学会学術集会
  • Place of Presentation: 長崎ブリックホール（長崎市）
  • Year and Date: 2016-12-10
• [Presentation] Tumor endothelial cells acquire drug resistance by exosomal-miR derived from high metastatic tumor (2016)
  • Author(s): Hida K., Torii C., Maishi N., Morimoto M., Akiyama K., Kawamoto T., Minami T., Yoshioka Y., Mohammad Towfik Alam, Shindoh M., Hida Y., Ochiya T
  • Organizer: The 19th International Vascular Biology Meeting
  • Place of Presentation: Sheraton Boston Hotel (USA)
  • Year and Date: 2016-11-02
  • Int'l Joint Research
• [Presentation] Tumor endothelial cells in high metastatic tumors promote metastasis via biglycan (2016)
  • Author(s): Maishi N., Ohba Y., Akiyama K., Ohga N., Hamada J., Nagao-Kitamoto H., Mohammad Towfik Alam, Shindoh M., Hida Y. Hida K.
  • Organizer: The 19th International Vascular Biology Meeting
  • Place of Presentation: Sheraton Boston Hotel (USA)
  • Year and Date: 2016-11-02
  • Int'l Joint Research
• [Presentation] P-glycoprotein expression dynamics in tumor blood vessels of urothelial carcinoma during chemotherapy (2016)
  • Author(s): Kikuchi H., Maishi N., Akiyama K., Morimoto M., Yanagiya M., Miyajima N., Tuchiya K., Maruyama S., Abe T., Hida Y., Harabayashi T., Ameda K., Matsumoto R., Kashiwagi A., Demura T., Tsuda M., Tanaka S., Matsuno Y., Shinohara N., Hida K.
  • Organizer: The 19th International Vascular Biology Meeting
  • Place of Presentation: Sheraton Boston Hotel (USA)
  • Year and Date: 2016-11-02
  • Int'l Joint Research
• [Presentation] 抗癌剤治療前後の尿路上皮癌における腫瘍血管内皮のP-glycoprotein発現変化 (2016)
  • Author(s): 菊地 央，間石奈湖，秋山廣輔，森本真弘，柳谷美沙，宮島直人，土屋邦彦，丸山 覚，安部崇重，樋田泰浩，原林 透，飴田 要，松本隆児，柏木 明，出村孝義，津田真寿美，田中伸哉，松野吉宏，篠原信雄，樋田京子
  • Organizer: 第49回北海道病理談話会
  • Place of Presentation: 北海道大学（札幌市）
  • Year and Date: 2016-10-15
• [Presentation] 口腔扁平上皮癌における腫瘍血管マーカーCXCR7の発現解析 (2016)
  • Author(s): 柳谷美沙，間石奈湖，鳥居ちさほ，樋田泰浩，大賀則孝，鄭 漢忠，進藤正信，北川善政，樋田京子
  • Organizer: 第49回北海道病理談話会
  • Place of Presentation: 北海道大学（札幌市）
  • Year and Date: 2016-10-15
• [Presentation] Tumor endothelial cells are resistant to acidic environments (2016)
  • Author(s): Annan Dorcas Akuba Muhyia，間石奈湖，曽我朋義，北條敬之，樋田泰浩，菊地 央，樋田京子
  • Organizer: 第49回北海道病理談話会
  • Place of Presentation: 北海道大学（札幌市）
  • Year and Date: 2016-10-15
• [Presentation] 高転移性腫瘍miRによる血管内皮におけるIL-6を介した薬剤耐性誘導 (2016)
  • Author(s): 間石奈湖，鳥居ちさほ，川本泰輔，秋山廣輔，吉岡祐亮，落谷孝広，柳谷美沙，森本真弘，菊地 央，鄭 漢忠，北川善政，進藤正信，樋田泰浩，樋田京子
  • Organizer: 第49回北海道病理談話会
  • Place of Presentation: 北海道大学（札幌市）
  • Year and Date: 2016-10-15
• [Presentation] 腫瘍血管内皮細胞によるがん転移促進 (2016)
  • Author(s): 間石奈湖，樋田京子
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（横浜市）
  • Year and Date: 2016-10-07
  • Invited
• [Presentation] 抗癌剤治療前後の尿路上皮癌における腫瘍血管内皮のP-glycoprotein 発現変化 (2016)
  • Author(s): 菊地 央，間石奈湖，土屋邦彦，丸山 覚，安部崇重，樋田泰浩，原林 透，松野吉宏，篠原信雄，樋田京子
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（横浜市）
  • Year and Date: 2016-10-07
• [Presentation] Tumor endothelial cells are resistant to acidic environments (2016)
  • Author(s): Dorcas A Annan, Maishi N., Soga T., Hida Y., Torii C., Kikuchi H., Hida K.
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（横浜市）
  • Year and Date: 2016-10-07
• [Presentation] 腫瘍血管内皮細胞によるbiglycanの分泌を介したがんの転移促進 (2016)
  • Author(s): 間石奈湖
  • Organizer: 平成28年度新学術領域研究「学術研究支援基礎形成【先端モデル動物支援プラットフォーム】」若手支援技術講習会
  • Place of Presentation: 蓼科グランドホテル滝の湯（長野県茅野市）
  • Year and Date: 2016-09-07
• [Presentation] 高転移性腫瘍miRによる血管内皮におけるIL-6を介した薬剤耐性誘導 (2016)
  • Author(s): 森本真弘，鳥居ちさほ，秋山廣輔，川本泰輔，間石奈湖，鄭漢忠，北川善政，進藤正信，樋田泰浩，樋田京子
  • Organizer: 第8回日本RNA-i研究会
  • Place of Presentation: グランドプリンスホテル広島（広島市）
  • Year and Date: 2016-09-02
• [Presentation] 活性酸素が腫瘍血管内皮細胞に及ぼす影響 (2016)
  • Author(s): 間石 奈湖、樋田 京子
  • Organizer: 第 69 回日本酸化ストレス学会学術集会
  • Place of Presentation: 仙台国際センター（仙台市）
  • Year and Date: 2016-08-31
  • Invited
• [Presentation] 抗癌剤治療前後の尿路上皮癌における腫瘍血管内皮のP-glycoprotein発現変化 (2016)
  • Author(s): 菊地 央，間石奈湖，秋山廣輔，樋田京子
  • Organizer: 第25回日本がん転移学会学術集会・総会
  • Place of Presentation: 米子コンベンションセンター（鳥取県米子市）
  • Year and Date: 2016-07-21
• [Presentation] 腫瘍血管内皮細胞によるbiglycanの分泌を介したがんの転移促進 (2016)
  • Author(s): 間石奈湖，秋山廣輔，大賀則孝，浜田淳一，樋田京子
  • Organizer: 第25回日本がん転移学会学術集会・総会
  • Place of Presentation: 米子コンベンションセンター（鳥取県米子市）
  • Year and Date: 2016-07-21
• [Presentation] 腫瘍血管内皮細胞によるがん転移促進 (2016)
  • Author(s): 間石奈湖
  • Organizer: 第12回北海道癌免疫制御研究会
  • Place of Presentation: メルキュールホテル札幌（札幌市）
  • Year and Date: 2016-07-09
  • Invited
• [Book] パラダイムシフトをもたらすエクソソーム機能研究最前線 (2017)
  • Author(s): 樋田京子，間石奈湖，森本真弘
  • Total Pages: 282
  • Publisher: エヌ・ティー・エス
• [Remarks] 北海道大学 遺伝子病制御研究所 フロンティア研究ユニット 血管生物学研究室ホームページ
  • URL: http://www.igm.hokudai.ac.jp/vascular-biology/