How cycling hypoxia initiates endothelial cell-macrophage cooperation to support tumor growth and metastasis

The different tumor microenvironment components, both cellular like
endothelial cells and 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 of endothelial cells on TAM.
Even less known is the influence of hypoxia, both cycling and chronic, on
these parameters. The objective of this project is to systematically study the
effects of both types of hypoxia on the inflammatory and angiogenic
phenotype of TAMs and on their interplay with endothelial cells. In
particular, we will focus on the influence of endothelial cells on the
polarization of TAMs and the outcomes for cancer cell invasiveness and
migration. Studies using an appropriate murine tumor model will be
developed in order to confirm in vitro results. All together, these results will
allow to better understand the dialog between the different cell types
present in tumors and the consequences of these interactions on tumor
growth and metastasis.