Effect of Hypoxia in endothelial cells.

• Project/Area Number: 24890009
• Research Category: Grant-in-Aid for Research Activity start-up
• Allocation Type: Single-year Grants
• Research Field: Surgical dentistry
• Research Institution: Hokkaido University
• Principal Investigator: KONDOH Miyako 北海道大学, 大学病院, 医員 (10631864)
• Project Period (FY): 2012-08-31 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 血管内皮細胞 / 低酸素 / 活性酸素 / 染色体異常 / 細胞 / 低酸素環境 / 染色体不安定性

Research Abstract

Tumor hypoxia is important for tumor progression. TECs upregulated several genes and have highly responsiveness to growth factor and resistant to some anti-cancer drugs. Furthermore, there is chromosomal abnormality in TECs. However the mechanism of acquisition of these abnormalities in TECs remains to be unknown. In this study, we investigated the effects of hypoxia on TEC abnormalities.
Under hypoxic condition, gene expressions of HIF-1 alpha and VEGFA in human NECs (HMVEC) were upregulated. Furthermore, the aneuploidy rate of NEC increased under hypoxia. In addition, ROS was elevated in NEC by hypoxia and inhibition of ROS by EGCG inhibited hypoxia-induced aneuploidy in HMVEC. VEGFR inhibitor also inhibited aneuploidy induced by hypoxia. These results suggest that hypoxic condition in tumor microenvironment might be one of mechanisms of acquisition of chromosomal abnormality in tumor endothelial cells.

Research Products

• [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, Towfik AM, Inoue N, Shindoh M, Hida K
  • Journal Title: PLOS ONE Volume: 8
  • NAID: 120005367415
  • Peer Reviewed
• [Journal Article] Lysyl oxidase secreted by tumour endothelial cells promotes angiogenesis and metastasis (2013)
  • Author(s): Osawa T, Ohga N, Akiyama K, Hida Y, Kitayama K, Kawamoto T, Yamamoto K, Maishi N, Kondoh M, Onodera Y, Fujie M, Nonomura K, Shindoh M, Hida K
  • Journal Title: Br J Cancer Volume: 109(8) Pages: 2237-2247
  • 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)
  • DOI: 10.1371/journal.pone.0080349
  • NAID: 120005367415
  • Peer Reviewed
• [Journal Article] Lysyl oxidase secreted by tumour endothelial cells promotes angiogenesis and metastasis (2013)
  • Author(s): Akiyama K.
  • Journal Title: Br J Cancer Volume: 63 Pages: 2237-2247
  • Peer Reviewed
• [Journal Article] Biglycan is a specific marker and an autocrine angiogenic factor of tumour endothelial cells (2012)
  • Author(s): Yamamoto 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(6) Pages: 1214-1223
  • Peer Reviewed
• [Journal Article] Tumor - derived microvesicles induce proangiogenic phenotype in endothelial cells via endocytosis (2012)
  • Author(s): Kawamoto T, Ohga N, Akiyama K, Hirata N, Kitahara S, Maishi N, Osawa T, Yamamoto K, Kondoh M, Shindoh M, Hida Y, Hida K
  • Journal Title: PLoS ONE Volume: 7(3)
  • NAID: 120005946706
  • 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, Hida K
  • Journal Title: Am J Pathol Volume: 180(3) Pages: 1283-1293
  • Peer Reviewed
• [Journal Article] Biglycan is a specific marker and an autocrine angiogenic factor of tumour endothelial cells. (2012)
  • Author(s): Yamamoto 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(6) Pages: 1214-1223
  • DOI: 10.1038/bjc.2012.59
  • Peer Reviewed
• [Journal Article] Tumor-derived microvesicles induce proangiogenic phenotype in endothelial cells via endocytosis (2012)
  • Author(s): T. Kawamoto, et al.
  • Journal Title: PLoS ONE Volume: 7
  • DOI: 10.1371/journal.pone.0034045
  • NAID: 120005946706
  • Peer Reviewed
• [Journal Article] Heterogeneity of Tumor Endothelial Cells: Comparison between Tumor Endothelial Cells Isolated from Highly Metastatic and Low Metastatic Tumo (2012)
  • Author(s): Ohga N
  • Journal Title: American Journal of Pathology Volume: 180(3) Pages: 1294-1307
  • DOI: 10.1016/j.ajpath.2011.11.035
  • 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): Akiyama K.
  • Journal Title: American Journal of Pathology Volume: 180(3) Pages: 1283-1293
  • DOI: 10.1016/j.ajpath.2011.11.029
  • Peer Reviewed
• [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92回北海道医学大会,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(札幌市)
  • Year and Date: 2012-09-08
• [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, The 10th Korea-Japan Joint Symposium on Vascular Biology
  • Place of Presentation: AWAGIN holl(Tokushima)
• [Presentation] Hypoxia induces angiogenic factors andaneuploidy in micirovascular endothelialcells (2012)
  • Author(s): Kondoh M
  • Organizer: The 20th annual Meeting of the Japanese Vascular Biology and MedicineOrganization, The 10th Korea-Japan Joint Symposium on Vascular Biology
  • 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
  • Organizer: 北海道癌談話会
  • Place of Presentation: 北大医学部学友会館フラテ（札幌）
• [Remarks] 北海道大学 血管生物学教室ホームページ
  • URL: http://www.den.hokudai.ac.jp/vascular-biology/