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Altered angiogenesis and survival in human tumor‐derived endothelial cells
Author(s) -
Bussolati Benedetta,
Deambrosis Ilaria,
Russo Simona,
Deregibus Maria Chiara,
Camussi Giovanni
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0557fje
Subject(s) - angiogenesis , autocrine signalling , tec , cancer research , biology , protein kinase b , vascular endothelial growth factor a , endothelial stem cell , in vivo , microbiology and biotechnology , vascular endothelial growth factor , neovascularization , receptor , in vitro , signal transduction , vegf receptors , biochemistry , genetics , ionosphere , physics , astronomy
ABSTRACT Knowledge on the functional properties of tumor‐derived endothelial cells (TEC) can be relevant for the development of antiangiogenic therapeutic strategies. In the present study, we obtained and characterized endothelial cell lines from human renal carcinomas. TEC did not undergo senescence and showed constant expression of markers of endothelial activation and angiogenesis. In vitro, TEC, in contrast to normal endothelial cells, were resistant to apoptosis, proadhesive for renal carcinoma cells, and able to grow and organize in the absence of serum in persistent capillary‐like structures. In vivo, TEC were able to grow in immunodeficient mice and to form vascular structures connected with the circulation. At a molecular level, gene array analysis showed an increased expression of genes involved in survival and cell adhesion compared with expression in normal microvascular endothelial cells. Moreover, expression of angiopoietin‐1 and vascular endothelial growth factor (VEGF)‐D and the Akt survival pathway were up‐regulated. Inhibition of interaction of VEGFR‐2 or VEGFR‐3 with VEGF‐D but not of Tie‐2‐angiopoietin‐1 interaction with soluble receptors abrogated Akt activation and survival of TEC. These results indicate that at least some of the TEC within a tumor display abnormal characteristics in terms of survival and angiogenic properties and also indicate the presence of a functional autocrine pathway related to VEGF‐D.