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Quantitative regulation of gene expression of human endothelial tumor markers by thrombospondin‐1 and nitric oxide crosstalk
Author(s) -
Li Dayan,
Isenberg Jeff S.,
Pendrak Michael L.,
Roberts David D.
Publication year - 2008
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/fasebj.22.1_supplement.782.30
Subject(s) - thrombospondin 1 , laminin , thrombospondin , extracellular matrix , angiogenesis , umbilical vein , basement membrane , microbiology and biotechnology , gene expression , biology , nitric oxide , chemistry , gene , cancer research , biochemistry , endocrinology , matrix metalloproteinase , in vitro , metalloproteinase
Angiogenesis, growth of new blood capillaries from existing vessels, is essential for progression of solid tumors. Thrombospondin‐1 (TSP1) is one of the most potent angiogenesis inhibitors and regulates nitric oxide (NO) signaling, which can be both inhibitory and stimulatory for blood vessel formation. Expression of several known tumor endothelium marker genes including extracellular matrix collagen Iα1, Iα2, IIIα1 genes, basement membrane collagen IVα1, laminin‐α3, and laminin‐α4 genes, and TEM8 was analyzed using quantitative RT‐PCR in human umbilical vein endothelial cells (HUVECs). Compared to untreated HUVEC and normalized to mRNA levels for the housekeeping gene hypoxanthine‐guanine phosphoribosyl transferase, mRNA levels of all of the tumor marker genes were downregulated 40 to 85% and 37 to 78% by exposure to exogenous TSP1 (2.2 nM) and NO donor DETA/NO (10 μM), respectively. When HUVECs were treated with both TSP1 and NO, mRNA expression of collagens Iα2, IIIα1, IVα1, laminin α3 and α4, and TEM8 rebounded toward control levels, indicating cross talk between TSP1 and NO in the coordinate regulation of these tumor endothelial markers.