Tumor cell invasion is the most critical step of metastasis. Determination of the mode of invasion within the particular tumor is critical for effective cancer treatment. Protease-independent amoeboid mode of invasion has been described in carcinoma cells and more recently in sarcoma cells on treatment with protease inhibitors. To analyze invasive behavior, we compared highly metastatic sarcoma cells with parental nonmetastatic cells. The metastatic cells exhibited a functional up-regulation of Rho/ROCK signaling and, similarly to carcinoma cells, an amoeboid mode of invasion. Using confocal and traction force microscopy, we showed that an up-regulation of Rho/ROCK signaling leads to increased cytoskeletal dynamics, myosin light chain localization, and increased tractions at the leading edge of the cells and that all of these contributed to increased cell invasiveness in a three-dimensional collagen matrix. We conclude that cells of mesenchymal origin can use the amoeboid nonmesenchymal mode of invasion as their primary invading mechanism and show the dependence of ROCK-mediated amoeboid mode of invasion on the increased capacity of cells to generate force.
- MeSH
- aktiny metabolismus MeSH
- buněčná adheze fyziologie MeSH
- čipová analýza proteinů MeSH
- cytoskelet metabolismus patologie MeSH
- faktory depolymerizující aktin metabolismus MeSH
- financování organizované MeSH
- fluorescenční mikroskopie MeSH
- fosforylace MeSH
- invazivní růst nádoru MeSH
- kinázy asociované s rho genetika metabolismus MeSH
- kolagen metabolismus MeSH
- krysa rodu rattus MeSH
- kultivované buňky MeSH
- lehké řetězce myosinu metabolismus MeSH
- Lim-kinasy genetika metabolismus MeSH
- magnetismus MeSH
- matrixová metaloproteinasa 2 metabolismus MeSH
- mezenchymální kmenové buňky metabolismus patologie MeSH
- pohyb buněk fyziologie MeSH
- rho proteiny vázající GTP genetika metabolismus MeSH
- sarkom metabolismus patologie MeSH
- upregulace MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
