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Contractility of the cell rear drives invasion of breast tumor cells in 3D Matrigel.

Abstract
Cancer cells use different modes of migration, including integrin-dependent mesenchymal migration of elongated cells along elements of the 3D matrix as opposed to low-adhesion-, contraction-based amoeboid motility of rounded cells. We report that MDA-MB-231 human breast adenocarcinoma cells invade 3D Matrigel with a characteristic rounded morphology and with F-actin and myosin-IIa accumulating at the cell rear in a uropod-like structure. MDA-MB-231 cells display neither lamellipodia nor bleb extensions at the leading edge and do not require Arp2/3 complex activity for 3D invasion in Matrigel. Accumulation of phospho-MLC and blebbing activity were restricted to the uropod as reporters of actomyosin contractility, and velocimetric analysis of fluorescent beads embedded within the 3D matrix showed that pulling forces exerted to the matrix are restricted to the side and rear of cells. Inhibition of actomyosin contractility or β1 integrin function interferes with uropod formation, matrix deformation, and invasion through Matrigel. These findings support a model whereby actomyosin-based uropod contractility generates traction forces on the β1 integrin adhesion system to drive cell propulsion within the 3D matrix, with no contribution of lamellipodia extension or blebbing to movement.
AuthorsRenaud Poincloux, Olivier Collin, Floria Lizárraga, Maryse Romao, Marcel Debray, Matthieu Piel, Philippe Chavrier
JournalProceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 108 Issue 5 Pg. 1943-8 (Feb 01 2011) ISSN: 1091-6490 [Electronic] United States
PMID21245302 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Drug Combinations
  • Integrin beta1
  • Laminin
  • Proteoglycans
  • matrigel
  • Collagen
  • Myosin Type II
Topics
  • Adenocarcinoma (pathology)
  • Breast Neoplasms (pathology)
  • Cell Line, Tumor
  • Cell Movement
  • Collagen
  • Drug Combinations
  • Female
  • Humans
  • Integrin beta1 (metabolism)
  • Laminin
  • Microscopy, Electron, Scanning
  • Microscopy, Electron, Transmission
  • Myosin Type II (metabolism)
  • Neoplasm Invasiveness
  • Proteoglycans

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