The Cancer Cell Oxygen Sensor PHD2 Promotes Metastasis via Activation of Cancer-Associated Fibroblasts
| Autor: | Massimiliano Mazzone, Anna Kuchnio, Ann Manderveld, Peter Carmeliet, Jean-Michel Foidart, Stijn Moens, Diether Lambrechts, Juan Ramon Hernandez-Fernaud, Sara Zanivan, An Carton, Bert Cruys, Stefan Vinckier, Françoise Bruyère, Carmen Bartic, Ulrike Bruning, Karol Kuchnio, Rodrigo Leite de Oliveira, Agnès Noël, Andreea Alexandra Ungureanu, Henar Cuervo, Mieke Dewerchin, Michaël Broux, Bernard Thienpont |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Contraction (grammar) Stromal cell Immunoblotting Biology Models Biological General Biochemistry Genetics and Molecular Biology Metastasis Cell Line Hypoxia-Inducible Factor-Proline Dioxygenases Mice Models Cell Line Tumor Neoplasms medicine Animals Humans Tumor growth Neoplasm Metastasis lcsh:QH301-705.5 Tumor Reverse Transcriptase Polymerase Chain Reaction Fibroblasts medicine.disease Biological Immunohistochemistry lcsh:Biology (General) Cell culture Immunology Cancer cell Cancer research Cancer-Associated Fibroblasts Female |
| Zdroj: | Cell Reports, Vol 12, Iss 6, Pp 992-1005 (2015) |
| ISSN: | 2211-1247 |
| Popis: | 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. publisher: Elsevier articletitle: The Cancer Cell Oxygen Sensor PHD2 Promotes Metastasis via Activation of Cancer-Associated Fibroblasts journaltitle: Cell Reports articlelink: http://dx.doi.org/10.1016/j.celrep.2015.07.010 content_type: article copyright: Copyright © 2015 The Authors. Published by Elsevier Inc. ispartof: Cell Reports vol:12 issue:6 pages:992-1005 ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
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