Hypoxia and hydrogen sulfide differentially affect normal and tumor-derived vascular endothelium.
endothelial cells play a key role in vessels formation both under physiological and pathological conditions. Their behavior is influenced by blood components including gasotransmitters (H2S, NO and CO). Tumor cells are subjected to a cyclic shift between pro-oxidative and hypoxic state and, in this scenario, H2S can be both cytoprotective and detrimental depending on its concentration. H2S effects on tumors onset and development is scarcely studied, particularly concerning tumor angiogenesis. We previously demonstrated that H2S is proangiogenic for tumoral but not for normal endothelium and this may represent a target for antiangiogenic therapeutical strategies.



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 H2S.



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. H2S neither affects cell viability nor prevents hypoxia and H2O2-induced damage. Endothelial migration is enhanced by hypoxia, while tubulogenesis is inhibited for all EC types. H2S acts differentially on EC migration and tubulogenesis.



these data provide evidence for a great variability of normal and altered endothelium in response to the environmental conditions.
Department of Life Sciences & Systems Biology, University of Torino, Italy. Electronic address: serena.bianco@unito.it.
Serena
S
Bianco
Department of Clinical and Biological Sciences, University of Torino, Italy. Electronic address: daniele.mancardi@unito.it.
Daniele
D
Mancardi
Department of Life Sciences & Systems Biology, University of Torino, Italy.
Annalisa
A
Merlino
Department of Molecular Biotechnology and Health Sciences, University of Torino, Italy. Electronic address: benedetta.bussolati@unito.it.
Benedetta
B
Bussolati
Department of Life Sciences & Systems Biology, University of Torino, Italy; Nanostructured Interfaces and Surfaces Centre of Excellence (NIS), University of Torino, Italy. Electronic address: luca.munaron@unito.it.
Luca
L
Munaron
D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000378:metabolism*; D018384:Oxidative Stress; D000072258:Tumor Hypoxia
D006862:Hydrogen Sulfide
Human breast carcinoma-derived EC; Human microvascular endothelial cells; Human renal carcinoma-derived EC; Hydrogen sulfide; Tumor angiogenesis