Extracellular matrix dynamics in cell migration, invasion and tissue morphogenesis

Abstract

This review describes how direct visualization of the dynamic interactions of cells with different extracellular matrix microenvironments can provide novel insights into complex biological processes. Recent studies have moved characterization of cell migration and invasion from classical 2D culture systems into 1D and 3D model systems, revealing multiple differences in mechanisms of cell adhesion, migration and signalling-even though cells in 3D can still display prominent focal adhesions.Myosin II restrains cell migration speed in 2D culture but is often essential for effective 3D migration. 3D cell migration modes can switch between lamellipodial, lobopodial and/or amoeboid depending on the local matrix environment. For example, "nuclear piston" migration can be switched off by local proteolysis, and proteolytic invadopodia can be induced by a high density of fibrillar matrix. Particularly, complex remodelling of both extracellular matrix and tissues occurs during morphogenesis. Extracellular matrix supports self-assembly of embryonic tissues, but it must also be locally actively remodelled. For example, surprisingly focal remodelling of the basement membrane occurs during branching morphogenesis-numerous tiny perforations generated by proteolysis and actomyosin contractility produce a microscopically porous, flexible basement membrane meshwork for tissue expansion. Cells extend highly active blebs or protrusions towards the surrounding mesenchyme through these perforations. Concurrently, the entire basement membrane undergoes translocation in a direction opposite to bud expansion. Underlying this slowly moving 2D basement membrane translocation are highly dynamic individual cell movements. We conclude this review by describing a variety of exciting research opportunities for discovering novel insights into cell-matrix interactions. K E Y W O R D S3D culture, basement membrane remodelling, branching morphogenesis, cell migration, extracellular matrix, invasion

Actin Remodeling Defects Leading to Autoinflammation and Immune Dysregulation

“…The local concentration of the complement system C3 fraction also contributes to this process ( 63 ). However, in 3D environment, the blebbing motility seems the more common migratory strategy of blood cells ( 64 , 65 ). Stop-codon variants of the CDC42 gene has been recently associated with a novel autoinflammatory disease characterized by neonatal-onset of cytopenia, rash, and hemophagocytosis (NOCARH), successfully treated with interleukin-1β inhibition (no.…”

Enhanced Malignant Phenotypes of Glioblastoma Cells Surviving NPe6-Mediated Photodynamic Therapy are Regulated via ERK1/2 Activation

“…Understanding and regulating the mechanisms underlying tumor cell invasiveness into the surrounding normal tissues have always been hurdles in the treatment of highly invasive malignant tumors, including GBMs. For invasion into adjacent tissues, the cells must migrate toward the neighboring normal tissues and degrade the ECM of adjacent cells; thus, targeting either or both of the machineries is considered crucial to prevent tumor cell invasion [44,45]. In the present study, suppression of the upregulated MAPK cascade inhibited the elevated migration capacity of GBM cells in the multiple migration assay but failed to block the augmented ECM degradation in NPe6-PDT-R cells, as evidenced by invadopodia assay.…”

Genetic interactions among ADAMTS metalloproteases and basement membrane molecules in cell migration inCaenorhabditis elegans

“…For example, cell surface expression of the integrin receptors that are required for cell migration may be reduced and, therefore, the DTC migration activity in gon-1 mutants may be weakened. Because the remodeling of the BM is coupled with epithelial cell migration [28, 29], reduced migration of DTCs could also lead to downregulation of BM remodeling, resulting in thick accumulation of collagen, which can further block DTC migration. Remodeling of the BM is likely to be mediated by the GON-1 protease activity.…”