Endothelial tip cells in vitro are less glycolytic and have a more flexible response to metabolic stress than non-tip cells.

Formation of new blood vessels by differentiated endothelial tip cells, stalk cells, and phalanx cells during angiogenesis is an energy-demanding process. How these specialized endothelial cell phenotypes generate their energy, and whether there are differences between these phenotypes, is unknown. This may be key to understand their functions, as (1) metabolic pathways are essentially involved in the regulation of angiogenesis, and (2) a metabolic switch has been associated with angiogenic endothelial cell differentiation. With the use of Seahorse flux analyses, we studied metabolic pathways in tip cell and non-tip cell human umbilical vein endothelial cell populations. Our study shows that both tip cells and non-tip cells use glycolysis as well as mitochondrial respiration for energy production. However, glycolysis is significantly lower in tip cells than in non-tip cells. Additionally, tip cells have a higher capacity to respond to metabolic stress. Finally, in non-tip cells, blocking of mitochondrial respiration inhibits endothelial cell proliferation. In conclusion, our data demonstrate that tip cells are less glycolytic than non-tip cells and that both endothelial cell phenotypes can adapt their metabolism depending on microenvironmental circumstances. Our results suggest that a balanced involvement of metabolic pathways is necessary for both endothelial cell phenotypes for proper functioning during angiogenesis.

Down-regulation of TSGA10, AURKC, OIP5 and AKAP4 genes by Lactobacillus rhamnosus GG and Lactobacillus crispatus SJ-3C-US supernatants in HeLa cell line.

BACKGROUND: Cancer testis antigens (CTAs) are considered cancer bio-markers due to their highly specific expression pattern in human malignancies and near absence from normal somatic tissues. Their specific expression has made them potential targets for early dia-gnosis, assessment of patients prognosis and treatment of cancer in recent years. Lactobacilli are a group of probio-tics with anti-cancer, immunomodulatory and other beneficial features. These bacteria have been shown to alter expression of several cancer-related genes. AIM: We investigated the effect of Lactobacillus rhamnosus GG supernatant (LRS) and Lactobacillus crispatus SJ-3C-US supernatant (LCS) on expression of four CTAs (TSGA10, AURKC, OIP5 and AKAP4) in HeLa cell line after synchronization using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and quantitative real-time polymerase chain reaction. RESULTS: LRS and LCS inhibited HeLa cell growth after 24 h as demonstrated by MTT assay. Expressions of all CTAs were down-regulated after treatment with both supernatants. CONCLUSION: This study showed the role of Lactobacilli in down-regulation of CTAs genes. Such expression change might be involved in the anticancer effects of these Lactobacilli. The underlying mechanisms of these observations are not clear but epigenetic modulatory mechanisms may participate in this process. Future studies are needed to assess functional roles of Lactobacilli in modulation of other cancer-related genes. Key words: probio-tic - cancer testis antigen - bio-marker - HeLa cell line.