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Zois, C.

Publications and source records attributed to Zois, C..

2 recordsLinked to original sources

Spatio-temporal dynamics of M1 and M2 macrophages in a multiphase model of tumor growth

This study investigates the complex dynamics of vascular tumors and their interplay with macrophages, key agents of the innate immune response. We model the tumor microenvironment as a multiphase fluid, with each cellular population treated as a distinct, non-mixing phase. The framework also incorporates diffusible species that are critical for processes such as nutrient transport, angio-genesis, chemotaxis, and macrophage activation. Numerical simulations of our model show how phenotypic and spatial heterogeneity in the macrophage population arises and how such heterogeneity impacts a tumors growth dynamics. Finally, we propose an immunotherapeutic strategy based on the experimental agent vactosertib which promotes an anti-tumor macrophage phenotype. Our simulations demonstrate an increased density of anti-tumor macrophages over the period of a few months, followed by a relapse period where the tumor regains its original dynamics.

bioengineering↗

Glutamine deprivation regulates the origin and function of cancer cell exosomes

Exosomes are secreted extracellular vesicles (EVs) carrying diverse cargos, which can modulate recipient cell behaviour. They are thought to derive from intraluminal vesicles formed in late endosomal multivesicular bodies (MVBs). An alternate exosome formation mechanism, which is conserved from fly to human, is described here, with exosomes carrying unique cargos, including the GTPase Rab11, generated in Rab11-positive recycling endosomal MVBs. Release of these exosomes from cancer cells is increased by reducing Akt/mechanistic Target of Rapamycin (mTORC1) signalling or depleting the key metabolic substrate glutamine, which diverts membrane flux through recycling endosomes. The resulting vesicles promote tumour cell proliferation and turnover, and modulate blood vessel networks in xenograft mouse models in vivo. Their growth-promoting activity, which is also observed in vitro, is Rab11a-dependent, involves ERK-MAPK-signalling and is inhibited by antibodies against Amphiregulin, an EGFR ligand concentrated on these vesicles. Therefore, glutamine depletion or mTORC1 inhibition stimulates release of Rab11a-exosomes with pro-tumorigenic functions, which we propose promote stress-induced tumour adaptation.

cancer biology↗