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.