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A 2B adenosine receptors promote tumor growth
Author(s) -
Ryzhov Sergey,
Novitskiy Sergey V.,
Zaynagetdinov Rinat,
Goldstein Anna E.,
Biaggioni Italo,
Dikov Mikhail M.,
Feoktistov Igor
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.898.16
Subject(s) - lewis lung carcinoma , adenosine , stimulation , adenosine receptor , receptor , vascular endothelial growth factor , downregulation and upregulation , endocrinology , extracellular , medicine , angiogenesis , chemistry , biology , vegf receptors , cancer research , metastasis , cancer , microbiology and biotechnology , agonist , biochemistry , gene
Due to rapid growth, solid tumors experience severe hypoxia and produce high levels of extracellular adenosine. We have previously shown that A 2B adenosine receptors (AR) upregulate VEGF and other angiogenic factors. To test the hypothesis that A 2B AR contribute to tumor growth, we used an isograft model of Lewis lung carcinoma (LLC) in A 2B AR knockout (A 2B KO) and control mice. We found that genetic ablation of A 2B AR in the host mice significantly increased median animal survival from 35 to 40 days. On day 14, tumor volume, weight, vascular density and VEGF protein levels were significantly lower in A 2B KO (by 48, 38, 30 and 41%, respectively), compared to control mice. Host‐derived CD45+ cells represented approximately 30% of total tumor cell populations in both A 2B KO and control mice. After MACS separation, tumor associated CD45+ cells isolated from A 2B KO mice produced significantly lower levels of VEGF (37±5 vs 149±8 pg/106 cells in control mice cells) when stimulated with the stable adenosine analog NECA (10 μ M ). In contrast, we found no difference in VEGF production between LLC CD45‐negative cells isolated from A 2B KO and control mice. We conclude that A 2B AR expressed on host CD45+ cells infiltrating LLC promote tumor vascularisation and growth, at least in part, by stimulation of VEGF production. Supported by NIH grants.