Compensation mechanism in tumor cell migration
Top Cited Papers
Open Access
- 13 January 2003
- journal article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 160 (2), 267-277
- https://doi.org/10.1083/jcb.200209006
Abstract
Invasive tumor dissemination in vitro and in vivo involves the proteolytic degradation of ECM barriers. This process, however, is only incompletely attenuated by protease inhibitor–based treatment, suggesting the existence of migratory compensation strategies. In three-dimensional collagen matrices, spindle-shaped proteolytically potent HT-1080 fibrosarcoma and MDA-MB-231 carcinoma cells exhibited a constitutive mesenchymal-type movement including the coclustering of β1 integrins and MT1–matrix metalloproteinase (MMP) at fiber bindings sites and the generation of tube-like proteolytic degradation tracks. Near-total inhibition of MMPs, serine proteases, cathepsins, and other proteases, however, induced a conversion toward spherical morphology at near undiminished migration rates. Sustained protease-independent migration resulted from a flexible amoeba-like shape change, i.e., propulsive squeezing through preexisting matrix gaps and formation of constriction rings in the absence of matrix degradation, concomitant loss of clustered β1 integrins and MT1-MMP from fiber binding sites, and a diffuse cortical distribution of the actin cytoskeleton. Acquisition of protease-independent amoeboid dissemination was confirmed for HT-1080 cells injected into the mouse dermis monitored by intravital multiphoton microscopy. In conclusion, the transition from proteolytic mesenchymal toward nonproteolytic amoeboid movement highlights a supramolecular plasticity mechanism in cell migration and further represents a putative escape mechanism in tumor cell dissemination after abrogation of pericellular proteolysis.Keywords
This publication has 59 references indexed in Scilit:
- β1 Integrin Is Not Essential for Hematopoiesis but Is Necessary for the T Cell-Dependent IgM Antibody ResponseImmunity, 2002
- Matrix Metalloproteinase Inhibitors and Cancer—Trials and TribulationsScience, 2002
- Cumulative Influence of Matrix Metalloproteinase-1 and -2 in the Migration of Melanoma Cells within Three-Dimensional Type I Collagen LatticesExperimental Cell Research, 2001
- Matrix-dependent Proteolysis of Surface Transglutaminase by Membrane-type Metalloproteinase Regulates Cancer Cell Adhesion and LocomotionPublished by Elsevier BV ,2001
- Integrin-ligand binding properties govern cell migration speed through cell-substratum adhesivenessNature, 1997
- Cell Migration: A Physically Integrated Molecular ProcessCell, 1996
- Tumor Cell Interactions with the Extracellular Matrix During Invasion and MetastasisAnnual Review of Cell Biology, 1993
- Fibroblasts retain their tissue phenotype when grown in three-dimensional collagen gels*1Experimental Cell Research, 1991
- Temporal relationships of F-actin bundle formation, collagen and fibronectin matrix assembly, and fibronectin receptor expression to wound contraction.The Journal of cell biology, 1990
- Lymphocyte migration into three-dimensional collagen matrices: a quantitative study.The Journal of cell biology, 1983