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  α5β1-integrin and MT1-MMP promote tumor cell migration in 2D but not in 3D fibronectin microenvironments

Corall, S., Haraszti, T., Bartoschik, T., Spatz, J. P., Ludwig, T., & Cavalcanti-Adam, E. A. (2014). α5β1-integrin and MT1-MMP promote tumor cell migration in 2D but not in 3D fibronectin microenvironments. Computational Mechanics, 53(3), 499-510. doi:10.1007/s00466-013-0960-6.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0015-8CE1-9 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002E-79D6-6
Genre: Journal Article

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 Creators:
Corall, Silke1, 2, Author              
Haraszti, Tamas1, 2, Author              
Bartoschik, Tanja, Author
Spatz, Joachim P.1, 2, Author              
Ludwig, Thomas, Author
Cavalcanti-Adam, Elisabetta Ada1, 2, Author              
Affiliations:
1Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society, ou_2364731              
2Biophysical Chemistry, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany, ou_persistent22              

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Free keywords: Cell migration; Fibronectin matrix; MT1-MMP; Integrins; Tumor microenvironment
 Abstract: Cell migration is a crucial event for physiological processes, such as embryonic development and wound healing, as well as for pathological processes, such as cancer dissemination and metastasis formation. Cancer cell migration is a result of the concerted action of matrix metalloproteinases (MMPs), expressed by cancer cells to degrade the surrounding matrix, and integrins, the transmembrane receptors responsible for cell binding to matrix proteins. While it is known that cell-microenvironment interactions are essential for migration, the role of the physical state of such interactions remains still unclear. In this study we investigated human fibrosarcoma cell migration in two-dimensional (2D) and three-dimensional (3D) fibronectin (FN) microenvironments. By using antibody blocking approach and cell-binding site mutation, we determined that α5β1-integrin is the main mediator of fibrosarcoma cell migration in 2D FN, whereas in 3D fibrillar FN, the binding of α5β1- and αvβ3-integrins is not necessary for cell movement in the fibrillar network. Furthermore, while the general inhibition of MMPs with GM6001 has no effect on cell migration in both 2D and 3D FN matrices, we observed opposing effect after targeted silencing of a membrane-bound MMP, namely MT1-MMP. In 2D fibronectin, silencing of MT1-MMP results in decreased migration speed and loss of directionality, whereas in 3D FN matrices, cell migration speed is increased and integrin-mediated signaling for actin dynamics is promoted. Our results suggest that the fibrillar nature of the matrix governs the migratory behavior of fibrosarcoma cells. Therefore, to hinder migration and dissemination of diseased cells, matrix molecules should be directly targeted, rather than specific subtypes of receptors at the cell membrane.

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Language(s): eng - English
 Dates: 2013-07-032013-12-102014-01-032014
 Publication Status: Published in print
 Pages: 12
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1007/s00466-013-0960-6
 Degree: -

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Title: Computational Mechanics
Source Genre: Journal
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Publ. Info: Berlin ; Heidelberg : Springer
Pages: - Volume / Issue: 53 (3) Sequence Number: - Start / End Page: 499 - 510 Identifier: ISSN: 0178-7675
CoNE: https://pure.mpg.de/cone/journals/resource/01787675