Glioblastoma cells block radiation-induced programmed cell death of endothelial cells

• Published in: FEBS letters Vol. 565; no. 1; pp. 167 - 170
• Main Authors: Brown, Charles K., Khodarev, Nikolai N., Yu, Jianqing, Moo-Young, Tricia, Labay, Edwardine, Darga, Thomas E., Posner, Mitchell C., Weichselbaum, Ralph R., Mauceri, Helena J.
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 07-05-2004
• Subjects: Apoptosis; Ataxia Telangiectasia Mutated Proteins; Blotting, Western; Cell Adhesion; Cell Cycle; Cell Cycle Proteins; Cell Division; Cell Line, Tumor; Cells, Cultured; Co-culture; Coculture Techniques; DNA array; DNA Repair; DNA repair and checkpoint gene; DNA, Complementary - metabolism; DNA-Activated Protein Kinase; DNA-Binding Proteins - metabolism; Endothelial cell survival; Endothelial Cells - pathology; Endothelial Cells - radiation effects; Endothelium, Vascular - cytology; Glioblastoma - pathology; Glioblastoma - radiotherapy; Green Fluorescent Proteins; Humans; Infrared Rays; Integrin alphaV - biosynthesis; Integrin alphaVbeta3 - metabolism; Integrin beta1 - biosynthesis; Luminescent Proteins - metabolism; Mitogen-Activated Protein Kinase 1 - metabolism; Nuclear Proteins; Oligonucleotide Array Sequence Analysis; Protein-Serine-Threonine Kinases - metabolism; Rad51 Recombinase; Radiotherapy; Recombination, Genetic; Transcription, Genetic; Transfection; Tumor Suppressor Proteins; Umbilical Veins - cytology; Up-Regulation; Vascular Endothelial Growth Factor A - metabolism; VEGF; DNA repair and checkpoint gene; Endothelial cell survival; Co-culture; DNA array; VEGF
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2004.03.099

We demonstrate that human umbilical vein endothelial cells (HUVEC) grown in co-culture (CC) with U87 glioblastoma cells transfected with green fluorescent protein (GFP-U87) exhibit resistance to radiation-mediated apoptosis. cDNA macroarray analysis reveals increases in the accumulation of RNAs for HUVEC genes encoding cell adhesion molecules, growth factor-related proteins, and cell cycle regulatory/DNA repair proteins. An increase in protein expression of integrin α
v, integrin β
1, MAPK(p42), Rad51, DNA-PK
CS, and ataxia telangiectasia gene (ATM) was detected in HUVEC grown in CC with GFP-U87 cells compared with HUVEC grown in mono-culture. Treatment with anti-VEGF antibody decreases the expression of integrin α
v, integrin β
1, DNA-PK
CS and ATM with a corresponding increase in ionizing radiation (IR)-induced apoptosis. These data support the concept that endothelial cells growing in the tumor microenvironment may develop resistance to cytotoxic therapies due to the up-regulation by tumor cells of endothelial cells genes associated with survival.