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

Abstract

Backgroundendothelial 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.Methodsin 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.Resultsall 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.Conclusionsthese data provide evidence for a great variability of normal and altered endothelium in response to the environmental conditions.

Purinergic Calcium Signals in Tumor-Derived Endothelium

“…Based on the dose-dependent amplitude and area of peak and plateau phases (Figure 1B,C), and according to the previously reported functional effects on BTEC migration [36], the following experiments were carried out treating BTEC with 100 μM ATP. Interestingly, renal tumor-derived endothelial cells (RTEC) (characterized in [39]), displayed a similar biphasic response to ATP (Figure S1A): moreover, their migration, similarly to BTEC, was affected by 100 μM ATP treatment (Figure S1B). When ATP was applied in a calcium-free extracellular solution (0 Ca out ), only a dose-dependent transient spike was detectable, due to Ca 2+ release from intracellular stores, while the plateau phase, mainly related to Ca 2+ entry from the extracellular medium, was completely abolished (Figure 1D–F).…”

Characterization of Osteogenesis and Chondrogenesis of Human Decellularized Allogeneic Bone with Mesenchymal Stem Cells Derived from Bone Marrow, Adipose Tissue, and Wharton’s Jelly

“…Suitable microporosity and mechanical strength of scaffolds are essential for osteogenesis and chondrogenesis. It has been known that pore sizes ranging from 200-350 µm are preferred for osteoblast growth, cell aggregation, and endothelial cell proliferation [17][18][19]. Moreover, a negative linear relationship between porosity and compressive strength was proposed [20].…”

P2X Purinergic Receptors Are Multisensory Detectors for Micro-Environmental Stimuli That Control Migration of Tumoral Endothelium

“…Indeed, the stroma of solid cancers is characterized by an accumulation of eATP [ 2 , 14 ], low oxygen levels-hypoxia [ 15 , 16 ], low pH-acidosis [ 17 , 18 , 19 , 20 ], the unbalance of Zn 2+ [ 21 , 22 ], Ca 2+ - hypercalcemia [ 23 , 24 ] and, at least in some particular tumors such as pancreatic ductal adeno-carcinoma (PDAC), mechanical alteration of the extracellular matrix resulting in increased stiffness [ 25 , 26 ]. The disordered composition and structure of the stroma is qualitatively and quantitatively variable among tissues and perturbs tumor growth and angiogenesis [ 27 , 28 , 29 , 30 , 31 , 32 ].…”