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

Title data

Corall, Silke ; Haraszti, Tamas ; Bartoschik, Tanja ; Spatz, Joachim Pius ; Ludwig, Thomas ; Cavalcanti-Adam, Elisabetta Ada:
α5β1-integrin and MT1-MMP promote tumor cell migration in 2D but not in 3D fibronectin microenvironments.
In: Computational Mechanics. Vol. 53 (2014) Issue 3 . - pp. 499-510.
ISSN 1432-0924

Abstract in another language

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.

Further data

Item Type: Article in a journal
Refereed: Yes
Institutions of the University: Faculties > Faculty of Engineering Science > Chair Cellular Biomechanics > Chair Cellular Biomechanics - Univ.-Prof. Dr. Dr. Elisabetta Ada Cavalcanti-Adam
Result of work at the UBT: No
DDC Subjects: 600 Technology, medicine, applied sciences > 620 Engineering
Date Deposited: 09 Jun 2023 10:34
Last Modified: 09 Jun 2023 10:34