Article (Scientific journals)
The Cancer Cell Oxygen Sensor PHD2 Promotes Metastasis via Activation of Cancer-Associated Fibroblasts.
Kuchnio, Anna; Moens, Stijn; Bruning, Ulrike et al.
2015In Cell Reports, 12 (6), p. 992-1005
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Abstract :
[en] Several questions about the role of the oxygen sensor prolyl-hydroxylase 2 (PHD2) in cancer have not been addressed. First, the role of PHD2 in metastasis has not been studied in a spontaneous tumor model. Here, we show that global PHD2 haplodeficiency reduced metastasis without affecting tumor growth. Second, it is unknown whether PHD2 regulates cancer by affecting cancer-associated fibroblasts (CAFs). We show that PHD2 haplodeficiency reduced metastasis via two mechanisms: (1) by decreasing CAF activation, matrix production, and contraction by CAFs, an effect that surprisingly relied on PHD2 deletion in cancer cells, but not in CAFs; and (2) by improving tumor vessel normalization. Third, the effect of concomitant PHD2 inhibition in malignant and stromal cells (mimicking PHD2 inhibitor treatment) is unknown. We show that global PHD2 haplodeficiency, induced not only before but also after tumor onset, impaired metastasis. These findings warrant investigation of PHD2's therapeutic potential.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Kuchnio, Anna
Moens, Stijn
Bruning, Ulrike
Kuchnio, Karol
Cruys, Bert
Thienpont, Bernard
Broux, Michael
Ungureanu, Andreea Alexandra
Leite de Oliveira, Rodrigo
Bruyere, Francoise
Cuervo, Henar
Manderveld, Ann
Carton, An
Hernandez-Fernaud, Juan Ramon
Zanivan, Sara
Bartic, Carmen
Foidart, Jean-Michel ;  Université de Liège > Département des sciences cliniques > Département des sciences cliniques
Noël, Agnès ;  Université de Liège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Vinckier, Stefan
Lambrechts, Diether
Dewerchin, Mieke
Mazzone, Massimiliano
Carmeliet, Peter
More authors (13 more) Less
Language :
English
Title :
The Cancer Cell Oxygen Sensor PHD2 Promotes Metastasis via Activation of Cancer-Associated Fibroblasts.
Publication date :
2015
Journal title :
Cell Reports
eISSN :
2211-1247
Publisher :
Elsevier
Volume :
12
Issue :
6
Pages :
992-1005
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2015 The Authors. Published by Elsevier Inc. All rights reserved.
Available on ORBi :
since 15 October 2015

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