JCB logo
Carestream Gel Logic 212PRO
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

Published online 13 January 2003. doi:10.1083/jcb.200209006
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 2465K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wolf, K.
Right arrow Articles by Friedl, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wolf, K.
Right arrow Articles by Friedl, P.
Related Collections
Right arrowRelated Article
Social Bookmarking
 Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

© The Rockefeller University Press, 0021-9525/2003/1/267 $5.00
The Journal of Cell Biology, Volume 160, Number 2, 267-277


Article

Compensation mechanism in tumor cell migration

: mesenchymal–amoeboid transition after blocking of pericellular proteolysis



Katarina Wolf1, Irina Mazo2, Harry Leung3, Katharina Engelke3, Ulrich H. von Andrian4, Elena I. Deryugina5, Alex Y. Strongin5, Eva-B. Bröcker1 and Peter Friedl1

1 Department of Dermatology, University of Würzburg, 97080 Würzburg, Germany
2 Department of Pediatrics, Children's Hospital
3 Department of Pathology, Harvard Medical School, Boston, MA 02115
4 Center for Blood Research, Harvard Medical School, Boston, MA 02115
5 The Burnham Institute, La Jolla, CA 92037

Address correspondence to P. Friedl, Department of Dermatology, University of Würzburg, Josef-Schneider-Str. 2, 97080 Würzburg, Germany. Tel.: 49-931-20126737. Fax: 49-931-20126700. E-mail: peter.fr{at}mail.uni-wuerzburg.de

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 ß1 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 ß1 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.

Key Words: cell migration; invasion; fibrosarcoma cells; carcinoma cells; matrix proteases


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?

Related Article

Tumor cells get primitive
Alan W. Dove
J. Cell Biol. 2003 160: 152. [Full Text] [PDF]



This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents