Effects of cycling hypoxia on tumor angiogenesis and inflammation
In collaboration with Prof. O. Feron (FATH, UCL)
The different tumor microenvironment components, both cellular like endothelial cells or tumor associated macrophages (TAMs) and physicochemical such as cycling or chronic hypoxia, all favor tumor development. Hypoxia initiates angiogenesis and the recruitment of monocytes, which will become TAMs. If these effects are now well described, few data are available regarding the reciprocal effects of TAMs on endothelial cells and angiogenesis and on cancer cell metastasis. Even less known is the influence of hypoxia, both cycling and chronic, on these parameters. The objective of this project is to study systematically the effects of both types of hypoxia on the influence of TAMs on cancer cell migration as well as on endothelial cells and their inflammatory and angiogenic phenotype. In parallel, the effects of cycling and chronic hypoxia will be investigated on the endothelial cells and on the effects that these cells have on TAMs, notably regarding their polarization. Studies on murine tumor models as well as on human tumor biopsies are developed in order to confirm in vitro results. All together, these results will allow to better understand the dialogue between the different cell types present in tumors and of the consequences of these interactions on tumor growth and metastasis.
Selected publications
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Michiels C, Tellier C & Feron O. 2016 ‘Cycling hypoxia: A key feature of the tumor microenvironment’ Biochimica Biophysica Acta, vol 1866, no. 1, pp. 76-86.
- Tellier, C, Desmet, D, Petit, L, Finet, L, Graux, C, Raes, M, Feron, O & Michiels, C 2015, 'Cycling hypoxia induces a specific amplified inflammatory phenotype in endothelial cells and enhances tumor-promoting inflammation in vivo' Neoplasia, vol 17, no. 1, pp. 66-78.
- Vegran, F, Boidot, R, Michiels, C, Sonveaux, P & Feron, O 2011, 'Lactate Influx through the Endothelial Cell Monocarboxylate Transporter MCT1 Supports an NF-kB/IL-8 Pathway that Drives Tumor Angiogenesis' Cancer Research, vol 71, no. 7, pp. 2550-2560.
- Toffoli, S, Roegiers, A, Feron, O, Van Steenbrugge, M, Ninane, N, Raes, M & Michiels, C 2009, 'Intermittent hypoxia is an angiogenic inducer for endothelial cells: role of HIF-1' Angiogenesis, vol 12, no. 1, pp. 47-67.
- Toffoli, S, Delaive, E, Dieu, M, Feron, O, Raes, M & Michiels, C 2009, 'NDRG1 and CRK-I/II are regulators of endothelial cell migration under intermittent hypoxia' Angiogenesis, vol 12, pp. 339-354.
- Toffoli, S & Michiels, C 2008, 'Intermittent hypoxia is a key regulator of cancer cell and endothelial cell interplay in tumours' FEBS Journal, vol 275, no. 12, pp. 2991-3002.
- Toffoli, S, Feron, O, Raes, M & Michiels, C 2007, 'Intermittent hypoxia changes HIF-1α phosphorylation pattern in endothelial cells: unravelling of a new PKA-dependent regulation of HIF-1α' Biochimica Biophysica Acta, vol 1773, no. 10, pp. 1558-1571.
- Martinive, P, Defresne, F, Bouzin, C, Saliez, J, Lair, F, Gregoire, V, Michiels, C, Dessy, C & Feron, O 2006, 'Preconditioning of the tumor vasculature and tumor cells by intermittent hypoxia: implications for anticancer therapies' Cancer Research, vol 66, no. 24, pp. 11736-11744.