A2B adenosine receptors promote tumor growth

Abstract

Due to rapid growth, solid tumors experience severe hypoxia and produce high levels of extracellular adenosine. We have previously shown that A2B adenosine receptors (AR) upregulate VEGF and other angiogenic factors. To test the hypothesis that A2BAR contribute to tumor growth, we used an isograft model of Lewis lung carcinoma (LLC) in A2BAR knockout (A2BKO) and control mice. We found that genetic ablation of A2BAR 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 A2BKO (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 A2BKO and control mice. After MACS separation, tumor associated CD45+ cells isolated from A2BKO 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 μM). In contrast, we found no difference in VEGF production between LLC CD45‐negative cells isolated from A2BKO and control mice. We conclude that A2BAR 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.