Tenascin-C orchestrates glioblastoma angiogenesis by modulation of pro- and anti-angiogenic signaling
Rupp T, Langlois B, Koczorowska MM, Radwanska A, Sun Z, Hussenet T, Lefebvre O, Murdamoothoo D, Arnold C, Klein A, Biniossek ML, Hyenne V, Naudin E, Velazquez-Quesada I, Schilling O, Van Obberghen-Schilling E, Orend G.
High expression of the extracellular matrix component tenascin-C in the tumor microenvironment cor- relates with decreased patient survival. Tenascin-C promotes cancer progression and a disrupted tumor vasculature through an unclear mechanism. Here, we examine the angiomodulatory role of tenascin-C. We find that direct contact of endothelial cells with tenascin-C disrupts actin polymerization, re- sulting in cytoplasmic retention of the transcriptional coactivator YAP. Tenascin-C also downregulates YAP pro-angiogenic target genes, thus reducing endothelial cell survival, proliferation, and tubulogen- esis. Glioblastoma cells exposed to tenascin-C secrete pro-angiogenic factors that promote endo- thelial cell survival and tubulogenesis. Proteomic analysis of their secretome reveals a signature, including ephrin-B2, that predicts decreased survival of glioma patients. We find that ephrin-B2 is an important pro-angiogenic tenascin-C effector. Thus, we demonstrate dual activities for tenascin-C in glioblastoma angiogenesis and uncover potential targeting and prediction opportunities.
