Relationship between metastasis of cancer and abnormality of tumor endothelial cell

• Project/Area Number: 23792306
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Hokkaido University
• Principal Investigator: NORITAKA Ohga 北海道大学, 歯学研究科(研究院), 助教 (40548202)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 腫瘍血管新生 / 転移 / 多様性 / 薬剤抵抗性 / 幹細胞性 / 腫瘍血管内皮細胞 / 腫瘍血管

Research Abstract

It is an important concept of tumor angiogenesis that tumor endothelial cells (TEC) are genetically normal and homogeneous. However, we had previously reported that TEC differ from normal endothelial cells (NEC). Whether the characteristics of TEC derived from different tumors differ remains unknown. To elucidate this, we isolated two types of TEC from highly metastatic tumor and low metastatic tumor and compared their characteristics. High metastatic tumor-derived TEC (HM-TEC) showed higher proliferative activity and invasive activity than low metastatic tumor-derived TEC (LM-TEC). Moreover, the mRNA expression levels of proangiogenic genes, such as VEGF-R1 and 2, VEGF and hypoxia (HIF-1) were higher in HM-TEC compared with those in LM-TEC. Furthermore, HM-TEC showed higher mRNA expression levels of the stemness-related genes compared with LM-TEC. These results indicate that TEC from high metastatic tumors have developed more abnormality than those from low metastatic tumors.

Research Products

• [Journal Article] Hypoxia -induced reactive oxygen species cause chromosomal abnormality of endothelial cells in tumor microenvironment (2013)
  • Author(s): Kondoh.M, Ohga.N., Akiyama.K, Hida.Y, Maishi.N, Alam Mohammad Towfik, Inoue.N, Shindoh.M, Hida.K.
  • Journal Title: PLoS ONE Volume: 8(11)
  • NAID: 120005367415
  • Peer Reviewed
• [Journal Article] Hypoxia-induced reactive oxygen species cause chromosomal abnormalities in endothelial cells in the tumor microenvironment (2013)
  • Author(s): Kondoh M., Ohga N., Akiyama K., Hida Y., Maishi N., Alam Mohammad Towfik, Inoue N., Shindoh M. and Hida K
  • Journal Title: PLoS ONE Volume: 8(11) Issue: 11 Pages: e80349-e80349
  • DOI: 10.1371/journal.pone.0080349
  • NAID: 120005367415
  • Peer Reviewed
• [Journal Article] Heterogeneity of Tumor Endothelial Cells : Comparison between Tumor Endothelial Cells Isolated from Highly Metastatic and Low Metastatic Tumors (2012)
  • Author(s): Ohga N., Ishikawa S., Maishi N., Akiyama K., Hida Y.,Kawamoto T., Sadamoto Y., Osawa T.,Yamamoto K., Kondoh M., Ohmura H., Shinohara N., Nonomura K., Shindoh M., Hida K.
  • Journal Title: Am J Pathol Volume: 180(3) Pages: 1294-1307
  • Peer Reviewed
• [Journal Article] Tumor endothelial cells acquire drug resistance by MDR1 upregulation via VEGF signaling in tumor microenvironment (2012)
  • Author(s): Akiyama K., Ohga N., Hida Y., Kawamoto T., Sadamoto Y., Ishikawa S., Maishi N., Akino T., Kondoh M., Matsuda A., Inoue N., Shindoh M. and Hida K.
  • Journal Title: Am J Pathol Volume: 180(3) Pages: 1283-1293
  • Peer Reviewed
• [Journal Article] Tumor endothelial cells acquire drug resistance by MDR1 upregulation via VEGF signaling in tumor microenvironment (2012)
  • Author(s): Akiyama K.
  • Journal Title: Am J Pathol Volume: 180(3) Issue: 3 Pages: 1283-1293
  • DOI: 10.1016/j.ajpath.2011.11.029
  • Peer Reviewed
• [Presentation] 転移能の異なる腫瘍由来の血管内皮の特性解析 (2012)
  • Author(s): 大賀則孝, 石川修平, 間石奈湖, 秋山廣輔, 樋田泰浩, 川本泰輔, 大村瞳, 進藤正信, 樋田京子
  • Organizer: 第23回日本臨床口腔病理学会総会・学術大会
  • Place of Presentation: 東京医科歯科大学鈴木章夫記念講堂(東京)
  • Year and Date: 2012-08-31
• [Presentation] 転移能の異なる腫瘍由来の血管内皮の特性解析 (2012)
  • Author(s): 大賀則孝, 石川修平, 樋田泰浩, 秋山廣輔, 間石奈湖, 川本泰輔, 進藤正信, 樋田京子
  • Organizer: 第28回日本DDS学会学術集会
  • Place of Presentation: 札幌コンベンションセンター(札幌)
  • Year and Date: 2012-07-03
• [Presentation] Hypoxia induces angiogenic factors andaneuploidy in micirovascular endothelialcells (2012)
  • Author(s): Kondoh M., Ohga N., Akiyama K., Maishi N., Kawamoto T., Hida Y., Shindoh M., Hida K.
  • Organizer: The 20th annual Meeting of the Japanese Vascular Biology and MedicineOrganization
  • Place of Presentation: あわぎんホール (徳島）
• [Presentation] 腫瘍内低酸素環境と腫瘍血管内皮の異常性の関連 (2012)
  • Author(s): 近藤美弥子、大賀則孝、樋田泰浩、秋山廣輔、間石奈湖、川本泰輔、進藤正信、樋田京子
  • Organizer: 第106回北海道癌談話会例会 腫瘍系分科会
  • Place of Presentation: 北海道大学医学部学友会館フラテ (札幌)
• [Presentation] 転移能の異なる腫瘍由来の血管内皮の特性解析 (2012)
  • Author(s): 大賀則孝
  • Organizer: 第23回日本臨床口腔病理学会総会・学術大会；学会奨励賞受賞者講演
  • Place of Presentation: 東京医科歯科大学 (東京)
  • Invited
• [Presentation] 転移能の異なる腫瘍由来の血管内皮の特性解析 (2012)
  • Author(s): 大賀則孝、石川修平、間石奈湖、秋山廣輔、樋田泰浩、川本泰輔、大村瞳、進藤正信、樋田京子
  • Organizer: 第23回日本臨床口腔病理学会総会・学術大会
  • Place of Presentation: 東京医科歯科大学 (東京)
• [Presentation] 転移能の異なる腫瘍から分離された腫瘍血管内皮細胞の比較解析, 腫瘍微小環境における腫瘍血管内皮異常性の獲得 (2011)
  • Author(s): 石川修平, 樋田泰浩, 秋山廣輔, 間石奈湖, 近藤美弥子, 川本泰輔, 進藤正信, 樋田京子
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋)
  • Year and Date: 2011-10-05
• [Presentation] 転移能の異なる腫瘍由来の血管内皮細胞の特性解析 (2011)
  • Author(s): 石川修平, 樋田泰浩, 秋山廣輔, 間石奈湖, 川本泰輔, 近藤美弥子, 進藤正信, 樋田京子
  • Organizer: 第91回北海道医学大会総会(第104回北海道癌談話会例会腫瘍分科会)
  • Place of Presentation: 札幌医科大学講堂(札幌)
  • Year and Date: 2011-09-17
• [Presentation] Comparative characterization of tumor endothelial cells isolated from highly and low metastatic tumors (2011)
  • Author(s): Ishikawa S., Hida Y., Akiyama K., Kitayama K., Kondoh M., Maishi N., Kawamoto T., Ohsawa T., Yamamoto K., Shindoh M., Hida K.
  • Organizer: The 5^<th> Meeting of Asian Society of Oral and Maxillofacial Pathology,"A New Insights into Tumor endothelial cell"
  • Place of Presentation: 九州大学医学部百年講堂(Fukuoka, Japan)
  • Year and Date: 2011-08-24
• [Presentation] 転移能の異なる腫瘍由来の血管内皮細胞の特性解析 (2011)
  • Author(s): 石川修平, 樋田泰浩, 間石奈湖, 川本泰輔, 秋山廣輔, 近藤美弥子, 進藤正信, 樋田京子
  • Organizer: 第20回日本がん転移学会学術集会・総会
  • Place of Presentation: アクトシティ浜松(浜松)
  • Year and Date: 2011-06-30
• [Presentation] Heterogeneity of Tumor Endothelial Cells : Comparison between Tumor Endothelial Cells Isolated from Highly Metastatic and Low Metastatic Tumors (2011)
  • Author(s): Ohga N., Ishikawa S., Maishi N., Akiyama K., Hida Y., Kawamoto T., Sadamoto Y., Kondoh M., Ohsawa T., Yamamoto K., Ohmura H., Shindoh M., Hida K.
  • Organizer: The 19th Annual Meeting of the Japanese Vascular Biology and Medicine Organization
  • Place of Presentation: 東京ステーションコンファレンス(Tokyo, Japan)
• [Presentation] 転移能の異なる腫瘍から分離された腫瘍血管内皮細胞の比較解析 (2011)
  • Author(s): 大賀則孝、石川修平、樋田泰浩、秋山廣輔、間石奈湖、近藤美弥子、川本泰輔、進藤正信、樋田京子
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
• [Presentation] Heterogeneity of Tumor Endothelial Cells:Comparison between Tumor Endothelial Cells Isolated from Highly Metastatic and Low Metastatic Tumors (2011)
  • Author(s): Ohga N., Ishikawa S., Maishi N., Akiyama K., Hida Y., Kawamoto T., Sadamoto Y., Kondoh M., Ohsawa T., Yamamoto K., Ohmura H., Shindoh M., Hida K
  • Organizer: The 19th Annual Meeting of the Japanese Vascular Biology and Medicine Organization
  • Place of Presentation: 東京ステージコンファレンス(東京)
• [Presentation] 前立腺とカテキン (2011)
  • Author(s): 大賀則孝、樋田京子
  • Organizer: 函館 Basic Cancer Forum(招待講演)
  • Place of Presentation: ベルコ函館(函館)
• [Remarks] 北海道大学 血管生物学教室
  • URL: http://www.den.hokudai.ac.jp/vascular-biology/
• [Remarks] 北海道大学 血管生物学教室
  • URL: http://www.den.hokudai.ac.jp/vascular-biology/
• [Remarks]
  • URL: http://www.den.hokudai.ac.jp/vascular-biology/