Hypoxia and hydrogen sulfide differentially affect normal and tumor-derived vascular endothelium.

Background: endothelial cells play a key role in vessels formation both under physiological and pathological conditions. Their behavior is influenced by blood components including gasotransmitters (HS, NO and CO). Tumor cells are subjected to a cyclic shift between pro-oxidative and hypoxic state and, in this scenario, HS can be both cytoprotective and detrimental depending on its concentration. HS effects on tumors onset and development is scarcely studied, particularly concerning tumor angiogenesis. We previously demonstrated that HS is proangiogenic for tumoral but not for normal endothelium and this may represent a target for antiangiogenic therapeutical strategies.

Methods: in this work, we investigate cell viability, migration and tubulogenesis on human EC derived from two different tumors, breast and renal carcinoma (BTEC and RTEC), compared to normal microvascular endothelium (HMEC) under oxidative stress, hypoxia and treatment with exogenous HS.

Results: all EC types are similarly sensitive to oxidative stress induced by hydrogen peroxide; chemical hypoxia differentially affects endothelial viability, that results unaltered by real hypoxia. HS neither affects cell viability nor prevents hypoxia and HO-induced damage. Endothelial migration is enhanced by hypoxia, while tubulogenesis is inhibited for all EC types. HS acts differentially on EC migration and tubulogenesis.

Conclusions: these data provide evidence for a great variability of normal and altered endothelium in response to the environmental conditions.