Tumor Vessel Normalization by Chloroquine Independent of Autophagy

作者：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 Marjan; Vion Anne Clemence; Radtke Freddy; Boulanger Chantal; Gerhardt Holger; Dejana Elisabetta; Dewerchin Mieke; Ghesquiere Bart; Annaert Wim; Agostinis Patrizia^*; Carmeliet Peter

来源：Cancer Cell, 2014, 26(2): 190-206.

DOI：10.1016/j.ccr.2014.06.025

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.

• 出版日期2014-8-11