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Title: How to teach an old dog new tricks: autophagy-independent action of chloroquine on the tumor vasculature
Authors: Maes, Hannelore
Kuchnio Anna, Anna
Carmeliet, Peter
Agostinis, Patrizia # ×
Issue Date: Nov-2014
Publisher: Landes Bioscience
Series Title: Autophagy vol:10 issue:11 pages:2082-2084
Article number: 10.4161/auto.36259
Abstract: Chloroquine (CQ) is exploited in clinical trials as an autophagy blocker to potentiate anticancer therapy, but it is unknown if it solely acts by inhibiting cancer cell-autonomous autophagy. Our recent study shows that besides blocking cancer cell growth, CQ also affects endothelial cells (ECs) and promotes tumor vessel normalization. This vessel normalizing effect of CQ reduces tumor hypoxia, cancer cell intravasation, and metastasis, while improving the delivery and response to chemotherapy. By compromising autophagy in melanoma cells or using mice with a conditional knockout of ATG5 in ECs, we found that the favorable effects of CQ on the tumor vasculature do not rely on autophagy. CQ-induced vessel normalization relies mainly on altered endolysosomal trafficking and sustained NOTCH1 signaling in ECs. Remarkably these CQ-mediated effects are abrogated when tumors are grown in mice harboring EC-specific deletion of NOTCH1. The autophagy-independent vessel normalization by CQ leading to improved delivery and tumor response to chemotherapy further advocates its clinical use in combination with anticancer treatments.
URI: 
ISSN: 1554-8627
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
Laboratory of Cell Death Research & Therapy
× corresponding author
# (joint) last author

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