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oai:repisalud.isciii.es:20.500.12105/172152024-09-21T09:29:07Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Kuchnio, Anna author Moens, Stijn author Bruning, Ulrike author Kuchnio, Karol author Cruys, Bert author Thienpont, Bernard author Broux, Michaël author Ungureanu, Andreea Alexandra author Leite de Oliveira, Rodrigo author Bruyère, Françoise author Cuervo, Henar author Manderveld, Ann author Carton, An author Hernandez-Fernaud, Juan Ramon author Zanivan, Sara author Bartic, Carmen author Foidart, Jean-Michel author Noel, Agnes author Vinckier, Stefan author Lambrechts, Diether author Dewerchin, Mieke author Mazzone, Massimiliano author Carmeliet, Peter author 2015-08-11 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. Cell Rep. 2015 Aug 11;12(6):992-1005. http://hdl.handle.net/20.500.12105/17215 26235614 10.1016/j.celrep.2015.07.010 2211-1247 Cell reports The Cancer Cell Oxygen Sensor PHD2 Promotes Metastasis via Activation of Cancer-Associated Fibroblasts.