Tumour-endothelium interactions in co-culture: Coordinated changes of gene expression profiles and phenotypic properties of endothelial cells

Nikolai N. Khodarev, Jianqing Yu, Edwardine Labay, Thomas Darga, Charles K. Brown, Helena J. Mauceri, Reza Yassari, Nalin Gupta, Ralph R. Weichselbaum

Research output: Contribution to journalArticle

134 Citations (Scopus)

Abstract

Tumour angiogenesis is a complex process based upon a sequence of interactions between tumour cells and endothelial cells. To model tumour/endothelial-cell interactions, we co-cultured U87 human glioma cells with human umbilical vein endothelial cells (HUVECs). U87 cells induced an 'activated' phenotype in HUVECs, including an increase in proliferation, migration and netlike formation. Activation was observed in co-cultures where cells were in direct contact and physically separated, suggesting an important role for soluble factor(s) in the phenotypic and genotypic changes observed. Expressional profiling of tumour-activated endothelial cells was evaluated using cDNA arrays and confirmed by quantitative PCR. Matching pairs of receptors/ligands were found to be coordinately expressed, including TGFβRII with TGFβ3, FGFRII and cysteine-rich fibroblast growth factor receptor (CRF-1) with FGF7 and FGF12, CCR1, CCR3, CCR5 with RANTES and calcitronin receptor-like gene (CALCRL) with adrenomedullin. Consistent with cDNA array data, immunohistochemical staining of expressed proteins revealed the upregulation of Tie-2 receptor in vitro and in vivo. Our data suggest that tumour-induced activation of quiescent endothelial cells involves the expression of angiogenesis-related receptors and the induction of autocrine growth loops. We suggest that tumour cells release growth factors that induce endothelial cells to express specific ligands and their cognate receptors coordinately.

Original languageEnglish (US)
Pages (from-to)1013-1022
Number of pages10
JournalJournal of Cell Science
Volume116
Issue number6
DOIs
StatePublished - Mar 15 2003
Externally publishedYes

Fingerprint

Coculture Techniques
Transcriptome
Endothelium
Endothelial Cells
Neoplasms
Human Umbilical Vein Endothelial Cells
Oligonucleotide Array Sequence Analysis
Receptor, Fibroblast Growth Factor, Type 1
Ligands
Adrenomedullin
Chemokine CCL5
Glioma
Cell Communication
Intercellular Signaling Peptides and Proteins
Up-Regulation
Staining and Labeling
Phenotype
Polymerase Chain Reaction
Growth
Genes

Keywords

  • Angiogenesis
  • Autocrine loops
  • Expressional profiling
  • Intercellular communication and activation

ASJC Scopus subject areas

  • Cell Biology

Cite this

Khodarev, N. N., Yu, J., Labay, E., Darga, T., Brown, C. K., Mauceri, H. J., ... Weichselbaum, R. R. (2003). Tumour-endothelium interactions in co-culture: Coordinated changes of gene expression profiles and phenotypic properties of endothelial cells. Journal of Cell Science, 116(6), 1013-1022. https://doi.org/10.1242/jcs.00281

Tumour-endothelium interactions in co-culture : Coordinated changes of gene expression profiles and phenotypic properties of endothelial cells. / Khodarev, Nikolai N.; Yu, Jianqing; Labay, Edwardine; Darga, Thomas; Brown, Charles K.; Mauceri, Helena J.; Yassari, Reza; Gupta, Nalin; Weichselbaum, Ralph R.

In: Journal of Cell Science, Vol. 116, No. 6, 15.03.2003, p. 1013-1022.

Research output: Contribution to journalArticle

Khodarev, Nikolai N. ; Yu, Jianqing ; Labay, Edwardine ; Darga, Thomas ; Brown, Charles K. ; Mauceri, Helena J. ; Yassari, Reza ; Gupta, Nalin ; Weichselbaum, Ralph R. / Tumour-endothelium interactions in co-culture : Coordinated changes of gene expression profiles and phenotypic properties of endothelial cells. In: Journal of Cell Science. 2003 ; Vol. 116, No. 6. pp. 1013-1022.
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