Compensation mechanism in tumor cell migration

By Katarina Wolf, I. Mazo, Harry Leung, K. Engelke, U. V. von Andrian, E. Deryugina, A. Strongin, E. Bröcker, Peter Friedl. Journal of Cell Biology, 2003

1,542 citations recorded by the source corpus.

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.

Subfields: Cancer Research, Cell Biology, Immunology and Allergy

View Paper: https://www.semanticscholar.org/paper/bba13d8ccc2f7dc22b93955dbfd7764c2561e8ad

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Citations in the corpus

Matrix metalloproteinases and tumor metastasis (2006, positive): “Importantly, this “mesenchymal-amoeboid transition” was observed also by intravital microscopy in a loose connective tissue of the mouse dermis [142], suggesting that this mechanism of motility transition may play a role during tumor progression to the invasive stage in vivo.”
Matrix metalloproteinases. (2010, positive): “Nevertheless, it is interesting to find that tumour cells may develop protease-independent migratory mechanisms in response to pericellular proteolysis blockage [136].”
Gelatinase-mediated migration and invasion of cancer cells. (2005, positive): “carcinoma cells can migrate in this manner (Wolf et al., 2003).”
Rac and Rho GTPases in cancer cell motility control (2010, background): “Beside environmental regulation, MAT can also be induced by epigenetic expression of regulating factors.”
Tumour-cell invasion and migration: diversity and escape mechanisms (2003, positive): “cgi?l=4323">MT1-MMP ), an important collagenase, and MMP2 co-localize with β1 or β3 integrins as they adhere to collagen fibre”
Cell–matrix adhesion (2007, background): “However, the requirement formatrix remodeling during tumor cell migration in vivo is controversial, since cells can reportedly shift between protease-dependent and independent migration modes (Friedl and Wolf, 2003; Wolf et al., 2003).”
The role of disturbed pH dynamics and the Na+/H+ exchanger in metastasis (2005, neutral): “First, there is a reduction in tumour-cell invasive capacity that is caused by increasing the pHe, by incubating the cells with a cocktail of inhibitors for various secreted protease”
Cell motility through plasma membrane blebbing (2008, background): “…blebbing also correlates with enhanced cell invasion ( Gadea et al., 2007 ; Kitzing et al., 2007 ; Tournaviti et al., 2007 ), suggesting that blebs exert additional functions beyond force generation to ensure pathfi nding of invading cells ( Sahai and Marshall, 2003 ; Wolf et al., 2003 ).”
Confinement and low adhesion induce fast amoeboid migration of slow mesenchymal cells. (2015, positive): “This phenomenon could also explain how inhibition ofmatrix-degrading enzymes such asMMPscould directly promote a switch to amoeboid migration by increasing the confinement of the growing tumor and/or of single migrating cells (Wolf et al., 2003).”