Isolated tumor endothelial cells maintain specific character during long-term culture

Kohei Matsuda, Noritaka Ohga, Yasuhiro Hida, Chikara Muraki, Kunihiko Tsuchiya, Takuro Kurosu, Tomoshige Akino, Shou Ching Shih, Yasunori Totsuka, Michael Klagsbrun, Masanobu Shindoh, Kyoko Hida

Research output: Contribution to journalArticlepeer-review

113 Citations (Scopus)

Abstract

Tumor angiogenesis is necessary for solid tumor progression and metastasis. Increasing evidence indicates that tumor endothelial cells (TECs) are more relevant to the study of tumor angiogenesis than normal endothelial cells (NECs) because their morphologies and gene expression are different from NECs. However, it is challenging to isolate and culture large numbers of pure ECs from tumor tissue since the percentage of ECs is only about 1-2% and tumor cells and fibroblasts easily overgrow them. In addition, there has been concern that isolated TECs may lose their special phenotype once they are dissociated from tumor cells. In this study, we have successfully purified murine TECs from four different human tumor xenografts and NECs from murine dermal tissue. Isolated ECs expressed endothelial markers, such as CD31, VE-cadherin (CD144), and endoglin (CD105), for more than 3 months after isolation. TECs maintained tumor endothelial-specific markers, such as tumor endothelial marker 8 (TEM8) and aminopeptidase N (APN), as in tumor blood vessels in vivo. In addition, TECs were more proliferative and motile than NECs. TECs showed a higher response to VEGF and higher expression of VEGF receptors-1 and -2 than NECs did. Stem cell antigen-1 was up-regulated in all four TECs, suggesting that they have a kind of stemness. Cultured TECs maintain distinct biological differences from NECs as in vivo. In conclusion, it was suggested that TECs are relevant material for tumor angiogenesis research.

Original languageEnglish
Pages (from-to)947-954
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume394
Issue number4
DOIs
Publication statusPublished - 16-04-2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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