CD73 on B16F10 melanoma cells in CD73-deficient mice promotes tumor growth, angiogenesis, neovascularization, macrophage infiltration and metastasis.

摘要: Ecto-5'-nucleotidase (CD73), an enzyme providing interstitial adenosine, mediates diverse physiological and pathological responses. In tumor progression, it has primarily immunosuppressive role but is also thought to regulate neovascularization. However, the latter still in debate. When B16F10 melanoma was subcutaneously injected into CD73 knockout mice, changes vasculature were not always observed. we demonstrated earlier that growth vascularization of mice depend on low presence cells. To further analyze vascularization, compared right flank wild-type lacking host only, with cell either inhibited AOPCP (adenosine α,β-methylene 5'-diphosphate) or permanently knocked down through genetic modification. We report here both inhibition knockdown alone. MAP-kinase signaling pathway activation decreased more strongly stable knockdown. There a significant reduction angiogenic blood microvessels as observed by anti-VEGFR2 staining. Stable reduced endothelial proliferation measured anti-CD105 only chemical significantly augmented intratumoral microvessel density induced knockout. Such when due much slower oxygen demand indicated expression Bad, hypoxia marker. Decreased activity led factors, including VEGF bFGF partially reversed tumors treated AOPCP. Both macrophage infiltration microenvironment changes, thereby influencing MI MII polarization. Additionally, important metastasis formation adenosine-independent attachment endothelium. conclude even undeniable regulation many aspects angiogenesis. thus viable target anti-angiogenic therapy.