論文

査読有り
2012年3月

Heterogeneity of Tumor Endothelial Cells Comparison between Tumor Endothelial Cells Isolated from High- and Low-Metastatic Tumors

AMERICAN JOURNAL OF PATHOLOGY
  • Noritaka Ohga
  • ,
  • Shuhei Ishikawa
  • ,
  • Nako Maishi
  • ,
  • Kosuke Akiyama
  • ,
  • Yasuhiro Hida
  • ,
  • Taisuke Kawamoto
  • ,
  • Yoshihiro Sadamoto
  • ,
  • Takahiro Osawa
  • ,
  • Kazuyuki Yamamoto
  • ,
  • Miyako Kondoh
  • ,
  • Hitomi Ohmura
  • ,
  • Nobuo Shinohara
  • ,
  • Katsuya Nonomura
  • ,
  • Masanobu Shindoh
  • ,
  • Kyoko Hida

180
3
開始ページ
1294
終了ページ
1307
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.ajpath.2011.11.035
出版者・発行元
ELSEVIER SCIENCE INC

An important concept in tumor angiogenesis is that tumor endothelial cells (TECs) are genetically normal and homogeneous. However, we previously reported that TECs differ from normal ECs. Whether the characteristics of TECs derived from different tumors differ remains unknown. To elucidate this, in this study, we isolated two types of TECs from high-metastatic (HM) and low-metastatic (LM) tumors and compared their characteristics. HM tumor-derived TECs (HM-TECs) showed higher proliferative activity and invasive activity than LM tumor-derived TECs (LM-TECs). Moreover, the mRNA expression levels of pro-angiogenic genes, such as vascular endothelial growth factor (VEGF) receptors 1 and 2, VEGF, and hypoxia-inducible factor-1 alpha, were higher in HM-TECs than in LM-TECs. The tumor blood vessels themselves and the surrounding area in HM tumors were exposed to hypoxia. Furthermore, HM-TECs showed higher mRNA expression levels of the sternness-related gene stem cell antigen and the mesenchymal marker CD90 compared with LM-TECs. HM-TECs were spheroid, with a smoother surface and higher circularity in the stem cell spheroid assay. HM-TECs differentiated into osteogenic cells, expressing activated alkaline phosphatase in an osteogenic medium at a higher rate than either LM-TECs or normal ECs. Furthermore, HM-TECs contained more aneuploid cells than LM-TECs. These results indicate that TECs from HM tumors have a more pro-angiogenic phenotype than those from LM tumors. (Am J Pathol 2012,180:1294-1307; DOI: 10.1016/j.ajpath.2011.11.035)

Web of Science ® 被引用回数 : 78

リンク情報
DOI
https://doi.org/10.1016/j.ajpath.2011.11.035
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/22245217
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000301022200040&DestApp=WOS_CPL

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