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Tumor vessel normalization by chloroquine independent of autophagy

Item Type:Article
Title:Tumor vessel normalization by chloroquine independent of autophagy
Creators Name:Maes, H. and Kuchnio, A. and Peric, A. and Moens, S. and Nys, K. and De Bock, K. and Quaegebeur, A. and Schoors, S. and Georgiadou, M. and Wouters, J. and Vinckier, S. and Vankelecom, H. and Garmyn, M. and Vion, A.C. and Radtke, F. and Boulanger, C. and Gerhardt, H. and Dejana, E. and Dewerchin, M. and Ghesquière, B. and Annaert, W. and Agostinis, P. and Carmeliet, P.
Abstract:Chloroquine (CQ) has been evaluated as an autophagy blocker for cancer treatment, but it is unknown if it acts solely by inhibiting cancer cell autophagy. We report that CQ reduced tumor growth but improved the tumor milieu. 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 and 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 anticancer treatment.
Keywords:Angiogenesis Inhibitors, Autophagy, Autophagy-Related Protein 5, Camptothecin, Cell Proliferation, Chloroquine, Drug Synergism, Endothelial Cells, Melanoma, Experimental, Microtubule-Associated Proteins, Neoplasm Invasiveness, Notch1 Receptor, Pathologic Neovascularization, Skin Neoplasms, Tumor Burden, Tumor Cell Line, Vascular Endothelium, Xenograft Model Antitumor Assays, Animals, Mice
Source:Cancer Cell
Publisher:Cell Press / Elsevier
Page Range:190-206
Date:11 August 2014
Official Publication:https://doi.org/10.1016/j.ccr.2014.06.025
PubMed:View item in PubMed

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