Dresden 2009 – wissenschaftliches Programm
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BP: Fachverband Biologische Physik
BP 4: Cell Mechanics
BP 4.6: Vortrag
Montag, 23. März 2009, 16:00–16:15, HÜL 186
Integrin expression increased contractile force generation that regulate cell invasion and tumor outgrowth — •Claudia Mierke1, Martina Fellner1, Benjamin Frey2, and Martin Herrmann2 — 1Universität Erlangen, Department für Physik, LS für Physikalisch-Medizinische Technik — 2Universitätsklinikum Erlangen, Innere Medizin 3, Erlangen, Germany
The process of metastasis formation includes cell invasion that causes malignant progression of tumors. The role of cell mechanics on the malignancy of tumor cells has not been investigated systematically. Highly-invasive tumor cells expressed significantly higher amounts of the a5b1 integrin compared to weakly-invasive. We hypothezise that high-a5b1 expressing cells increase contractile force generation that increased cell invasion into a collagen matrix. Our results show that high a5b1 integrin expression increased cell invasiveness and increased the contractile force generation. Whether the increased contractile force generation is a prerequiste for enhanced cell invasiveness, we inhibited the invasiveness through blocking of the myosin light chain kinase by ML-7 or ROCK kinase by Y27632. Indeed, the reduction of contractile force decreased the cell invasiveness. Furthermore, we analyzed whether high-a5b1 and low-a5b1 cells formed tumor in nude mice. The tumor formation/ growth is impared in high-a5b1 compared to low-a5b1 cells. The integrin a5b1 acts as enhancer of cell invasiveness where contractile forces are necessary to overcome the viscous drag, but as suppressor of primary tumor formation/ growth where increased motility is rather a hindrance for cell clustering to form solid tumors.