The use of mixed collagen-Matrigel matrices of increasing complexity recapitulates the biphasic role of cell adhesion in cancer cell migration: ECM sensing, remodeling and forces at the leading edge of cancer invasion

Autor: Carlos Castilla, Cristina Ederra, M. Mora, Martín Martínez, José Manuel García Aznar, Maria Anguiano, Xabier Morales, Alejandro Rodríguez Pena, Nieves Movilla, Maider Esparza, Iván Cortés-Domínguez, Mikel Ariz, Carlos Ortiz-de-Solorzano, H. Amaveda
Rok vydání: 2020
Předmět:
0301 basic medicine
Integrins
Microfluidics
Gene Expression
Mechanotransduction
Cellular
Biochemistry
Extracellular matrix
0302 clinical medicine
Cell Movement
Tumor Microenvironment
Mechanotransduction
Materials
Multidisciplinary
biology
Chemistry
Integrin beta1
Physics
Cell migration
Condensed Matter Physics
Extracellular Matrix
Cancer Cell Migration
Cell biology
Drug Combinations
Cell Motility
030220 oncology & carcinogenesis
Physical Sciences
Engineering and Technology
Medicine
Proteoglycans
Collagen
Fluidics
Cellular Structures and Organelles
Research Article
Surface Properties
Amorphous Solids
Science
Materials Science
Material Properties
Integrin
Respiratory Mucosa
Cell Migration
Models
Biological
Focal adhesion
03 medical and health sciences
Cell Line
Tumor
Cell Adhesion
Humans
Cell adhesion
Focal Adhesions
Tumor microenvironment
Matrigel
Biology and Life Sciences
Proteins
Epithelial Cells
Cell Biology
030104 developmental biology
Mixtures
biology.protein
Anisotropy
Laminin
Gels
Collagens
Developmental Biology
Zdroj: Zaguán. Repositorio Digital de la Universidad de Zaragoza
instname
PLoS ONE, Vol 15, Iss 1, p e0220019 (2020)
PLoS ONE
ISSN: 1932-6203
Popis: The migration of cancer cells is highly regulated by the biomechanical properties of their local microenvironment. Using 3D scaffolds of simple composition, several aspects of cancer cell mechanosensing (signal transduction, EMC remodeling, traction forces) have been separately analyzed in the context of cell migration. However, a combined study of these factors in 3D scaffolds that more closely resemble the complex microenvironment of the cancer ECM is still missing. Here, we present a comprehensive, quantitative analysis of the role of cell-ECM interactions in cancer cell migration within a highly physiological environment consisting of mixed Matrigel-collagen hydrogel scaffolds of increasing complexity that mimic the tumor microenvironment at the leading edge of cancer invasion. We quantitatively show that the presence of Matrigel increases hydrogel stiffness, which promotes β1 integrin expression and metalloproteinase activity in H1299 lung cancer cells. Then, we show that ECM remodeling activity causes matrix alignment and compaction that favors higher tractions exerted by the cells. However, these traction forces do not linearly translate into increased motility due to a biphasic role of cell adhesions in cell migration: at low concentration Matrigel promotes migration-effective tractions exerted through a high number of small sized focal adhesions. However, at high Matrigel concentration, traction forces are exerted through fewer, but larger focal adhesions that favor attachment yielding lower cell motility.
Databáze: OpenAIRE
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