TY - JOUR
T1 - Tumour-endothelium interactions in co-culture
T2 - Coordinated changes of gene expression profiles and phenotypic properties of endothelial cells
AU - Khodarev, Nikolai N.
AU - Yu, Jianqing
AU - Labay, Edwardine
AU - Darga, Thomas
AU - Brown, Charles K.
AU - Mauceri, Helena J.
AU - Yassari, Reza
AU - Gupta, Nalin
AU - Weichselbaum, Ralph R.
PY - 2003/3/15
Y1 - 2003/3/15
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Autocrine loops
KW - Expressional profiling
KW - Intercellular communication and activation
UR - http://www.scopus.com/inward/record.url?scp=0037444476&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037444476&partnerID=8YFLogxK
U2 - 10.1242/jcs.00281
DO - 10.1242/jcs.00281
M3 - Review article
C2 - 12584245
AN - SCOPUS:0037444476
SN - 0021-9533
VL - 116
SP - 1013
EP - 1022
JO - Journal of cell science
JF - Journal of cell science
IS - 6
ER -