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Title: Discontinuation of anti-VEGF cancer therapy promotes metastasis through a liver revascularization mechanism.
Authors: Yang, Y.
Zhang, Y.
Iwamoto, H.
Hosaka, K.
Seki, T.
Andersson, P.
Lim, S.
Fischer, C.
Nakamura, M.
Abe, M.
Cao, R.
Skov, P. V.
Chen, F.
Chen, X.
Lu, Y.
Nie, G.
Cao, Yihai
First Published: 1-Sep-2016
Publisher: Nature Publishing Group
Citation: Nature Communications, 2016, 7:12680
Abstract: The impact of discontinuation of anti-VEGF cancer therapy in promoting cancer metastasis is unknown. Here we show discontinuation of anti-VEGF treatment creates a time-window of profound structural changes of liver sinusoidal vasculatures, exhibiting hyper-permeability and enlarged open-pore sizes of the fenestrated endothelium and loss of VE-cadherin. The drug cessation caused highly leaky hepatic vasculatures permit tumour cell intravasation and extravasation. Discontinuation of an anti-VEGF antibody-based drug and sunitinib markedly promotes liver metastasis. Mechanistically, host hepatocyte, but not tumour cell-derived vascular endothelial growth factor (VEGF), is responsible for cancer metastasis. Deletion of hepatocyte VEGF markedly ablates the 'off-drug'-induced metastasis. These findings provide mechanistic insights on anti-VEGF cessation-induced metastasis and raise a new challenge for uninterrupted and sustained antiangiogenic therapy for treatment of human cancers.
DOI Link: 10.1038/ncomms12680
eISSN: 2041-1723
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
Description: The authors declare that the data supporting the findings of this study are available within the article and its Supplementary Information files.
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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