title: How tumour-induced vascular changes alter angiogenesis: Insights from a computational model.
abstract: A computational model was developed to describe experimentally observed vascular changes induced by the introduction of a tumour on a mouse equipped with a dorsal skinfold chamber. The vascular structure of the host tissue was segmented from in vivo images and transposed into the computational framework. Simulations of tumour-induced vascular changes were performed and include the destabilizing effects of the growth factor VEGF on the integrity of the vessels walls. The integration of those effects, that include alteration of the vessel wall elasticity and wall breaching, were required to realistically reproduce the experimental observations. The model was then used to investigate the importance of the vascular changes for oxygen delivery and tumour development. To that end, we compared simulations obtained with a dynamic vasculature with those obtained with a static one. The results showed that the tumour growth was strongly impeded by the constant vascular changes. More precisely, it is the angiogenic process itself that was affected by vascular changes occurring in bigger upstream vessels and resulting in a less efficient angiogenic network for oxygen delivery. As a consequence, tumour cells are mostly kept in a non-proliferative hypoxic state. Tumour dormancy thus appears as one potential consequence of the intense vascular changes in the host tissue.
authors.affiliation: Université Grenoble Alpes, CNRS, Laboratory TIMC-IMAG/DyCTIM2, UMR 5525, 38041 Grenoble, France. Electronic address: angelique.stephanou@imag.fr.
authors.forename: A
authors.initials: A
authors.lastname: Stéphanou
authors.affiliation: Université Grenoble Alpes, CNRS, Laboratory TIMC-IMAG/DyCTIM2, UMR 5525, 38041 Grenoble, France.
authors.forename: A C
authors.initials: AC
authors.lastname: Lesart
authors.affiliation: Ecrins Therapeutics, BIOPOLIS, 38700 La Tronche, France.
authors.forename: J
authors.initials: J
authors.lastname: Deverchère
authors.affiliation: Ecrins Therapeutics, BIOPOLIS, 38700 La Tronche, France.
authors.forename: A
authors.initials: A
authors.lastname: Juhem
authors.affiliation: Ecrins Therapeutics, BIOPOLIS, 38700 La Tronche, France.
authors.forename: A
authors.initials: A
authors.lastname: Popov
authors.affiliation: Université Grenoble Alpes, EA 7442 RSRM, ID17-ESRF, 38000 Grenoble, France.
authors.forename: F
authors.initials: F
authors.lastname: Estève
mesh_terms: D000465:Algorithms; D000818:Animals; D003198:Computer Simulation; D008819:Mice, Nude; D008954:Models, Biological; D009369:Neoplasms / Q000098:blood supply* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D010100:Oxygen / Q000378:metabolism; D013997:Time Factors; D059016:Tumor Microenvironment; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D010100:Oxygen
keywords: Angiogenesis; Hybrid model; Hypoxia; Quiescence; Vascular changes