CD44 Interacts with HIF-2α to Modulate the Hypoxic Phenotype of Perinecrotic and Perivascular Glioma Cells.

Autor:	Johansson E; Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Scheelevägen 2, Medicon Village 404:C3, 223 63 Lund, Sweden., Grassi ES; Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Scheelevägen 2, Medicon Village 404:C3, 223 63 Lund, Sweden., Pantazopoulou V; Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Scheelevägen 2, Medicon Village 404:C3, 223 63 Lund, Sweden., Tong B; Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Scheelevägen 2, Medicon Village 404:C3, 223 63 Lund, Sweden., Lindgren D; Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Scheelevägen 2, Medicon Village 404:C3, 223 63 Lund, Sweden., Berg TJ; Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Scheelevägen 2, Medicon Village 404:C3, 223 63 Lund, Sweden., Pietras EJ; Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen 2200, Denmark., Axelson H; Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Scheelevägen 2, Medicon Village 404:C3, 223 63 Lund, Sweden., Pietras A; Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Scheelevägen 2, Medicon Village 404:C3, 223 63 Lund, Sweden. Electronic address: alexander.pietras@med.lu.se.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2017 Aug 15; Vol. 20 (7), pp. 1641-1653.
DOI:	10.1016/j.celrep.2017.07.049
Abstrakt:	Hypoxia-inducible factors enhance glioma stemness, and glioma stem cells have an amplified hypoxic response despite residing within a perivascular niche. Still, little is known about differential HIF regulation in stem versus bulk glioma cells. We show that the intracellular domain of stem cell marker CD44 (CD44ICD) is released at hypoxia, binds HIF-2α (but not HIF-1α), enhances HIF target gene activation, and is required for hypoxia-induced stemness in glioma. In a glioma mouse model, CD44 was restricted to hypoxic and perivascular tumor regions, and in human glioma, a hypoxia signature correlated with CD44. The CD44ICD was sufficient to induce hypoxic signaling at perivascular oxygen tensions, and blocking CD44 cleavage decreased HIF-2α stabilization in CD44-expressing cells. Our data indicate that the stem cell marker CD44 modulates the hypoxic response of glioma cells and that the pseudo-hypoxic phenotype of stem-like glioma cells is achieved by stabilization of HIF-2α through interaction with CD44, independently of oxygen. (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu