Title: Tumor vessel normalization by chloroquine independent of autophagy
Authors: Maes, Hannelore *
Kuchnio, Anna *
Peric, Aleksandar
Moens, Stijn
Nys, Kris
De Bock, Katrien
Quaegebeur, Annelies
Schoors, Sandra
Georgiadou, Maria
Wouters, Jasper
Vinckier, Stefan
Vankelecom, Hugo
Garmyn, Maria
Vion, Anne-Clémence
Boulanger, Chantal
Gerhardt, Holger
Dejana, Elisabetta
Dewerchin, Mieke
Ghesquière, Bart
Annaert, Wim
Agostinis, Patrizia ×
Carmeliet, Peter #
Issue Date: 11-Aug-2014
Publisher: Cell Press
Series Title: Cancer Cell vol:26 issue:2 pages:190-206
Abstract: Chloroquine (CQ) is evaluated as autophagy-blocker for cancer treatment, but it is unknown if it solely acts by inhibiting cancer cell autophagy. We report that CQ reduced tumor growth but improved the tumor microenvironment. By normalizing tumor vessel structure and function and increasing perfusion, CQ reduced hypoxia, cancer cell invasion and metastasis, while improving chemotherapy delivery and response. Inhibiting autophagy in cancer cells or endothelial cells (ECs) failed to induce such effects. CQ’s vessel normalization activity relied mainly on alterations of endosomal Notch1 trafficking / signaling in ECs and was abrogated by Notch1 deletion in ECs in vivo. Thus, autophagy-independent vessel normalization by CQ restrains tumor invasion and metastasis while improving chemotherapy, supporting the use of CQ for anti-cancer treatment.
ISSN: 1535-6108
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Cell Death Research & Therapy
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
Laboratory of Membrane Trafficking
Translational Research in GastroIntestinal Disorders
Exercise Physiology Research Group
Translational Cell & Tissue Research
Stem Cell Biology and Embryology (+)
Laboratory of Dermatology
Vascular Patterning Laboratory (Vesalius Research Center) (+)
Department of Human Genetics - miscellaneous
* (joint) first author
× corresponding author
# (joint) last author

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