Berlin 2008 – wissenschaftliches Programm

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BP: Fachverband Biologische Physik

BP 1: Cell Migration and Tissue Dynamics

BP 1.6: Vortrag

Montag, 25. Februar 2008, 11:30–11:45, C 243

Cell migration through connective tissue in 3-D — •Claudia Tanja Mierke, Philip Kollmannsberger, Thorsten Koch, Daniel Paranhos-Zitterbart, and Ben Fabry — Universität Erlangen, Biophysik, Erlangen, Deutschland

A prerequisite for metastasis formation is the ability of tumor cells to invade and migrate through connective tissue. We analyzed the role of matrix-degrading enzymes, adhesion receptor expression, contractile force generation, and remodeling of cytoskeletal structures for cell invasiveness. We studied 51 well-established tumor cell lines regarding their ability to migrate through a collagen matrix. 27 cell lines were found to be non-invasive, and 24 cell lines were invasive to different degrees that we quantified by the number density of cells that invaded into the gels, multiplied with the average invasion depth. 2-D and 3-D traction microscopy was used to measure contractile forces. Adhesion strengths, cytoskeletal stiffness and molecular turn-over rates were measured using magnetic tweezer microrheology. The speed of cytoskeletal remodelling processes was characterized using nanoscale particle tracking. MMP-14 matrix metalloproteinase and 14 integrin adhesion receptor expression was measured using FACS analysis. We found that cell invasiveness correlated with increased expression of MMP-14 matrix metalloproteinase and integrin receptors (alpha3 and 5), increased contractile force generation, and increased speed of cytoskeletal reorganization. In summary, our results may help identify molecules and signal transduction pathways that control tumor invasion and metastasis formation.