Gradient-induced instability in tumour spheroids unveils the impact of microenvironmental nutrient changes.

Autor: Ascione F; Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, P. Le V. Tecchio 80, 80125, Naples, Italy., Ferraro R; Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, P. Le V. Tecchio 80, 80125, Naples, Italy.; CEINGE Advanced Biotechnologies Franco Salvatore, Via G. Salvatore 436, 80131, Naples, Italy., Dogra P; Mathematics in Medicine Program, Department of Medicine, Houston Methodist Research Institute, Houston, TX, 77030, USA.; Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY, 10065, USA., Cristini V; Mathematics in Medicine Program, Department of Medicine, Houston Methodist Research Institute, Houston, TX, 77030, USA.; Neal Cancer Center, Houston Methodist Research Institute, Houston, TX, 77030, USA.; Department of Imaging Physics, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.; Physiology, Biophysics, and Systems Biology Program, Graduate School of Medical Sciences, Weill Cornell Medicine, New York, NY, 10065, USA., Guido S; Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, P. Le V. Tecchio 80, 80125, Naples, Italy.; CEINGE Advanced Biotechnologies Franco Salvatore, Via G. Salvatore 436, 80131, Naples, Italy., Caserta S; Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, P. Le V. Tecchio 80, 80125, Naples, Italy. sergio.caserta@unina.it.; CEINGE Advanced Biotechnologies Franco Salvatore, Via G. Salvatore 436, 80131, Naples, Italy. sergio.caserta@unina.it.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Sep 06; Vol. 14 (1), pp. 20837. Date of Electronic Publication: 2024 Sep 06.
DOI: 10.1038/s41598-024-69570-6
Abstrakt: Tumours often display invasive behaviours that induce fingering, branching and fragmentation processes. The phenomenon, known as diffusional instability, is driven by differential cell proliferation, migration, and death due to the presence of metabolite and catabolite concentration gradients. An understanding of the intricate dynamics of this spatially heterogeneous process plays a key role in the investigation of tumour growth and invasion. In this study, we developed an in vitro tumour invasion assay to investigate cell invasiveness in tumour spheroids under a chemotactic stimulus. Our method, employing tumour spheroids seeded in a 3D collagen gel within a microfluidic chemotaxis chamber, focuses on the role of diffusive gradients. Using Time-Lapse Microscopy, the dynamic evolution of tumour spheroids was monitored in real-time, providing a comprehensive view of the morphological changes and cell migration patterns under different chemotactic conditions. Specifically, we explored the impact of fetal bovine serum (FBS) gradients on the behaviour of CT26 mouse colon carcinoma cells and compared the effects of varying FBS concentrations to two isotropic control conditions. Furthermore, a finite element in silico model was developed to quantify the diffusive flow of nutrients in the chemotaxis chamber and obtain a detailed understanding of tumour dynamics. Our findings reveal that the presence of a chemotactic gradient significantly influences tumour invasiveness, with higher concentrations of nutrients associated with increased cancer growth and cell migration.
(© 2024. The Author(s).)
Databáze: MEDLINE
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