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  • Dynamic stroma reorganization drives blood vessel dysmorphia during glioma growth.

Dynamic stroma reorganization drives blood vessel dysmorphia during glioma growth.

EMBO molecular medicine (2017-10-19)
Thomas Mathivet, Claire Bouleti, Matthias Van Woensel, Fabio Stanchi, Tina Verschuere, Li-Kun Phng, Joost Dejaegher, Marly Balcer, Ken Matsumoto, Petya B Georgieva, Jochen Belmans, Raf Sciot, Christian Stockmann, Massimiliano Mazzone, Steven De Vleeschouwer, Holger Gerhardt
ABSTRACT

Glioma growth and progression are characterized by abundant development of blood vessels that are highly aberrant and poorly functional, with detrimental consequences for drug delivery efficacy. The mechanisms driving this vessel dysmorphia during tumor progression are poorly understood. Using longitudinal intravital imaging in a mouse glioma model, we identify that dynamic sprouting and functional morphogenesis of a highly branched vessel network characterize the initial tumor growth, dramatically changing to vessel expansion, leakage, and loss of branching complexity in the later stages. This vascular phenotype transition was accompanied by recruitment of predominantly pro-inflammatory M1-like macrophages in the early stages, followed by