Year: 2022
Type: preprint
Abstract: Cell proliferation and invasion are two key drivers of tumor progression and are traditionally considered two independent cellular processes regulated by distinct pathways. Through in vitro and in silico methods, we provide evidence that these two processes are intrinsically coupled through matrix-adhesion friction. Using novel tumor spheroids, we show that both tumor cell proliferation and invasion are limited by a volumetric carrying capacity of the system, i.e. maximum spatial cell concentration supported by the system’s total cell count, nutrient consumption rate, and collagen gel mechanical properties. To manipulate these phenotypes in breast cancer cells, we modulate the expression of E-cadherin and its associated role in adhesion, invasion, and proliferation. We integrate these results into a mixed-constitutive formulation to computationally delineate the contributions of cellular and extracellular adhesion, stiffness, and mechanical properties of the extracellular matrix (ECM) to the proliferative and invasive fates of breast cancer tumor spheroids. Both approaches conclude that the dominant drivers of tumor fate are system properties modulating cell-ECM friction, such as E-cadherin dependent cell-ECM adhesion and matrix pore size.
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
Funders: Ministerio de Ciencia, Innovación y Universidades, European Commission, Universidad Carlos III de Madrid, European Regional Development Fund, Agencia Estatal de Investigación, National Institute on Aging, National Cancer Institute, National Institute of Arthritis and Musculoskeletal and Skin Diseases, H2020 European Research Council, Ministerio de Universidades
Awards: G1297238948, G1622782223, G1912770925, G2262748287, G2648084224, Single-cell phenotyping for therapeutic stratification in pancreatic cancer, G3480869486, G4042783231, G434337789, Biomechanical Stimulation based on 4D Printed Magneto-Active Polymers, G5080475149, G5404395142, G5555131222, G5967599077, G601512365, G7084143925, G7573077907, G7805626310, G8497050386, G8684520763, Center for 3D Imaging in Cancer Cell Biology
OpenAlex ID: W4309231127