title: PDGF‑stimulated dispersal of cell clusters and disruption of fibronectin matrix on three-dimensional collagen matrices requires matrix metalloproteinase-2.
abstract: Formation of cell clusters is a common morphogenic cell behavior observed during tissue and organ development and homeostasis, as well as during pathological disorders. Dynamic regulation of cell clustering depends on the balance between contraction of cells into clusters and migration of cells as dispersed individuals. Previously we reported that under procontractile culture conditions, fibronectin fibrillar matrix assembly by human fibroblasts functioned as a nucleation center for cell clustering on three-dimensional collagen matrices. Here we report that switching preformed cell clusters from procontractile to promigratory culture conditions results in cell dispersal out of clusters and disruption of FN matrix. Experiments using small interfering RNA silencing and pharmacological inhibition demonstrated that matrix metalloproteinase activity involving MMP-2 was necessary for fibronectin matrix disruption and dispersal of cell clusters.
authors.affiliation: Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX 75390-9039.
authors.forename: Bruno
authors.initials: B
authors.lastname: da Rocha-Azevedo
authors.affiliation: Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX 75390-9039.
authors.forename: Chin-Han
authors.initials: CH
authors.lastname: Ho
authors.affiliation: Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX 75390-9039 frederick.grinnell@utsouthwestern.edu.
authors.forename: Frederick
authors.initials: F
authors.lastname: Grinnell
mesh_terms: D002449:Cell Aggregation; D002460:Cell Line; D003470:Culture Media / Q000737:chemistry; D005109:Extracellular Matrix / Q000378:metabolism; D024022:Fibrillar Collagens / Q000737:chemistry*; D005347:Fibroblasts / Q000201:enzymology*; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000502:physiology*
chemical_list: D003470:Culture Media; D024022:Fibrillar Collagens; D005353:Fibronectins; D010982:Platelet-Derived Growth Factor; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2