The integrin alphav beta3 increases cellular stiffness and cytoskeletal remodeling dynamics to facilitate cancer cell invasion

Claudia Tanja Mierke
2013 New Journal of Physics  
Hans Kubitschke et al -The size-speed-force relationship governs migratory cell response to tumorigenic factors Aldo Leal-Egaña et al -This content was downloaded from IP address 207.241.231.81 on 25/07/2018 at 16:35 Abstract. The process of cancer cell invasion through the extracellular matrix (ECM) of connective tissue plays a prominent role in tumor progression and is based fundamentally on biomechanics. Cancer cell invasion usually requires cell adhesion to the ECM through the cell-matrix
more » ... h the cell-matrix adhesion receptors integrins. The expression of the αvβ3 integrin is increased in several tumor types and is consistently associated with increased metastasis formation in patients. The hypothesis was that the αvβ3 integrin expression increases the invasiveness of cancer cells through increased cellular stiffness, and increased cytoskeletal remodeling dynamics. Here, the invasion of cancer cells with different αvβ3 integrin expression levels into dense three-dimensional (3D) ECMs has been studied. Using a cell sorter, two subcell lines expressing either high or low amounts of αvβ3 integrins (αvβ3 high or αvβ3 low cells, respectively) have been isolated from parental MDA-MB-231 breast cancer cells. αvβ3 high cells showed a threefold increased cell invasion compared to αvβ3 low cells. Similar results were obtained for A375 melanoma, 786-O kidney and T24 bladder carcinoma cells, and cells in which the β3 integrin subunit was knocked down using specific siRNA. To investigate whether contractile forces are essential for αvβ3 integrin-mediated increased cellular stiffness and subsequently enhanced
doi:10.1088/1367-2630/15/1/015003 fatcat:4rxzr2sulfe2xbqsp3hr7o5uai