Discontinuation of anti-VEGF cancer therapy promotes metastasis through a liver revascularization mechanism

Yang, YL (author)

Iwamoto, H (author)

Nakamura, M (author)

Abe, M (author)

Skov, PV (author)

Chen, F (author)

Chen, XY (author)

Lu, YT (author)

Nie, GH (author)

(creator_code:org_t)

2016-09-01
2016
English.
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 12680-

Related links:: https://doi.org/10.1...; show more...; http://kipublication...; https://doi.org/10.1...; show less...

Abstract Subject headings

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.

By the author/editor: Yang, YL; Zhang, Y; Iwamoto, H; Hosaka, K; Seki, T; Andersson, P; show more...; Lim, S; Fischer, C; Nakamura, M; Abe, M; Cao, RH; Skov, PV; Chen, F; Chen, XY; Lu, YT; Nie, GH; Cao, YH; show less...

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.