Journal
FEBS LETTERS
Volume 580, Issue 14, Pages 3395-3400Publisher
WILEY
DOI: 10.1016/j.febslet.2006.05.011
Keywords
angiogenesis; hypoxia; endothelial cell; gene expression; tumor marker
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By triggering an adaptive response to hypoxia which is a common feature of tumor microenvironments, endothelial cells contribute to the onset of angiogenic responses involved in tumor growth. Therefore, identifying hypoxic markers represent a challenge for a better understanding of tumor angiogenesis and for the optimization of anti-angiogenic therapeutic strategy. Using representational difference analysis combined with microarray, we here report the identification of 133 hypoxia-induced transcripts in human microendothelial cells (HMEC-1). By Northern blot, we confirm hypoxia-induced expression of insulin-like growth factor binding protein 3 (igfbp3), thioredoxin-interacting protein (txnip), neuritin (nrn1). Finally, by performing in situ hybridization on several types of human tumors, we provide evidence for nrn1 and txnip as hypoxic perinecrotic markers and for igfbp3 as a tumor endothelial marker. We propose these hypoxia-induced genes could represent relevant prognostic tools and targets for therapeutic intervention in cancers. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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