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Publications

by Keyword: Collective invasion

Cicconofri, Giancarlo, Blanco, Pau, Vilanova, Guillermo, Saez, Pablo, Arroyo, Marino, (2024). Active interfacial degradation/deposition of an elastic matrix by a fluid inclusion: Theory and pattern formation Journal Of The Mechanics And Physics Of Solids 191, 105773

During collective invasion in 3D, cohesive cellular tissues migrate within a fibrous extracellular matrix (ECM). This process requires significant remodeling of the ECM by cells, notably proteolysis at the cell-ECM interface by specialized molecules. Motivated by this problem, we develop a theoretical framework to study the dynamics of a fluid inclusion (modeling the cellular tissue) embedded in an elastic matrix (the ECM), which undergoes surface degradation/deposition. To account for the active nature of this process, we develop a continuum theory based on irreversible thermodynamics, leading to a kinetic relation for the degradation front that locally resembles the force-velocity relation of a molecular motor. We further study the effect of mechanotransduction on the stability of the cell-ECM interface, finding a variety of self- organized dynamical patterns of collective invasion. Our work identifies ECM proteolysis as an active process possibly driving the self-organization of cellular tissues.

JTD Keywords: Accretion, Accretion and erosion, Active matter, Cell-migration, Collective invasion, Growth, Insight, Irreversible thermodynamics, Mechanics, Model, Morphogenesis, Moving non-material interfaces, Pattern formatio, Proteolysis, Surface, Surface growth


Conti, S, Kato, T, Park, D, Sahai, E, Trepat, X, Labernadie, A, (2021). CAFs and cancer cells co-migration in 3D spheroid invasion assay Crispr Knock-Ins In Organoids To Track Tumor Cell Subpopulations 2179, 243-256

© 2020, Springer Science+Business Media, LLC, part of Springer Nature. In many solid tumors, collective cell invasion prevails over single-cell dissemination strategies. Collective modes of invasion often display specific front/rear cellular organization, where invasive leader cells arise from cancer cell populations or the tumor stroma. Collective invasion involves coordinated cellular movements which require tight mechanical crosstalk through specific combinations of cell–cell interactions and cell–matrix adhesions. Cancer Associated Fibroblasts (CAFs) have been recently reported to drive the dissemination of epithelial cancer cells through ECM remodeling and direct intercellular contact. However, the cooperation between tumor and stromal cells remains poorly understood. Here we present a simple spheroid invasion assay to assess the role of CAFs in the collective migration of epithelial tumor cells. This method enables the characterization of 3D spheroid invasion patterns through live cell fluorescent labeling combined with spinning disc microscopy. When embedded in extracellular matrix, the invasive strands of spheroids can be tracked and leader/follower organization of CAFs and cancer cells can be quantified.

JTD Keywords: 3d spheroid invasion, cancer associated fibroblasts, collective migration, dissemination, epithelial cancer cells, leader/follower cells, 3d spheroid invasion, Cancer associated fibroblasts, Cancer-associated fibroblasts, Cell culture techniques, Cell line, tumor, Cell movement, Cell tracking, Collective invasion, Collective migration, Epithelial cancer cells, Extracellular matrix, Humans, Imaging, three-dimensional, Leader/follower cells, Microscopy, fluorescence, Spheroids, cellular, Tumor cells, cultured