Emerging evidence implicates sphingosine-1-phosphate [[signaling]] in the [[pathobiology]] of [[glioblastoma]] and [[angiogenesis]], but its role in glioblastoma-endothelial [[crosstalk]] remains largely unknown. In a study, Hadi et al., from Department of Medical Biotechnology and Translational Medicine, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico [[Milan]], Laboratory of General Physiology, Department of Biology and Biotechnology "Lazzaro Spallanzani", University of [[Pavia]], [[Italy]], sought to determine whether the crosstalk between glioblastoma cells and brain [[endothelial cell]]s regulates sphingosine-1-phosphate signaling in the [[tumor microenvironment]]. Using human glioblastoma and brain endothelial cell lines, as well as primary brain endothelial cells derived from human glioblastoma, they report that glioblastoma-co-culture promotes the expression, activity, and plasma membrane enrichment of sphingosine kinase 2 in brain endothelial cells, leading to increased cellular level of sphingosine-1-phosphate, and significant potentiation of its secretion. In turn, extracellular sphingosine-1-phosphate stimulates glioblastoma cell proliferation, and brain endothelial cells migration and angiogenesis. They also showed that, after co-culture, glioblastoma cells exhibit enhanced expression of [[S1P1]] and [[S1P3]], the sphingosine-1-phosphate receptors that are of paramount importance for cell growth and invasivity. Collectively, the results envision glioblastoma-endothelial crosstalk as a multi-compartmental strategy to enforce pro-tumoral sphingosine-1-phosphate signaling in the glioblastoma microenvironment
((Hadi LA, Anelli V, Guarnaccia L, Navone S, Beretta M, Moccia F, Tringali C,
Urechie V, Campanella R, Marfia G, Riboni L. A bidirectional crosstalk between
glioblastoma and brain endothelial cells potentiates the angiogenic and
proliferative signaling of sphingosine-1-phosphate in the glioblastoma
microenvironment. Biochim Biophys Acta. 2018 Jul 26. pii: S1388-1981(18)30177-X. 
doi: 10.1016/j.bbalip.2018.07.009. [Epub ahead of print] PubMed PMID: 30056170.
)).