title: Hydrogen sulfide promotes calcium signals and migration in tumor-derived endothelial cells.
abstract: Hydrogen sulfide (H(2)S) is a gasotransmitter that plays several roles in various tissues, including the cardiovascular system. Because it has been recently proposed to act as a mediator of angiogenesis progression, here we investigate the effects of H(2)S in a well-established model of tumor angiogenesis: endothelial cells obtained from human breast carcinoma (B-TECs). Ca(2+) imaging and patch-clamp experiments reveal that acute perfusion with NaHS, a widely employed H(2)S donor, activates cytosolic calcium (Ca(c)) increase, as well as potassium and nonselective cationic currents, in B-TECs. Stimulation with NaHS in the same concentration range (1 nM-200 μM) evoked Ca(c) signals also in "normal" human microvascular endothelial cells (HMVECs), but the amplitude was significantly lower. Moreover, although NaHS failed to promote either migration or proliferation on HMVECs, B-TEC migration was enhanced at low-micromolar NaHS concentrations (1-10 μM). Remarkably H(2)S mediates tumor proangiogenic signaling triggered by vascular endothelial growth factor (VEGF). B-TECs pretreated with dl-propargylglycine (5mM, 30 min), an inhibitor of the H(2)S-producing enzyme cystathionine γ-lyase, showed drastically reduced migration and Ca(c) signals induced by VEGF (20 ng/ml). We conclude that H(2)S plays a role in proangiogenic signaling of tumor-derived but not normal human ECs. Furthermore the ability of this gasotransmitter to interfere with B-TEC responsiveness to VEGF suggests that it could be an interesting target for antiangiogenic strategies in tumor treatment.
authors.affiliation: Department of Animal and Human Biology, University of Torino, 10123 Torino, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Pupo
authors.forename: Alessandra Fiorio
authors.initials: AF
authors.lastname: Pla
authors.forename: Daniele
authors.initials: D
authors.lastname: Avanzato
authors.forename: Francesco
authors.initials: F
authors.lastname: Moccia
authors.forename: José-Everardo Avelino
authors.initials: JE
authors.lastname: Cruz
authors.forename: Franco
authors.initials: F
authors.lastname: Tanzi
authors.forename: Annalisa
authors.initials: A
authors.lastname: Merlino
authors.forename: Daniele
authors.initials: D
authors.lastname: Mancardi
authors.forename: Luca
authors.initials: L
authors.lastname: Munaron
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002118:Calcium / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured
chemical_list: D002118:Calcium; D006862:Hydrogen Sulfide