Up-regulation of Rho/ROCK signaling in sarcoma cells drives invasion and increased generation of protrusive forces.
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.
Rösel
Daniel
D
Department of Cell Biology, Faculty of Science, Charles University in Prague, Czech Republic.
Brábek
Jan
J
Tolde
Ondrej
O
Mierke
Claudia T
CT
Zitterbart
Daniel P
DP
Raupach
Carina
C
Bicanová
Krisýtyna
K
Kollmannsberger
Philip
P
Panková
Daniela
D
Vesely
Pavel
P
Folk
Petr
P
Fabry
Ben
B
D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism / Q000473:pathology*; D054461:Lim Kinases / Q000235:genetics / Q000378:metabolism; D008280:Magnetics; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology; D008856:Microscopy, Fluorescence; D018994:Myosin Light Chains / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D040081:Protein Array Analysis; D051381:Rats; D012509:Sarcoma / Q000378:metabolism* / Q000473:pathology*; D015854:Up-Regulation; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism*
D051339:Actin Depolymerizing Factors; D000199:Actins; D018994:Myosin Light Chains; C076659:myosin light chain I; D003094:Collagen; D054461:Lim Kinases; C515894:Limk1 protein, rat; D054460:rho-Associated Kinases; D020778:Matrix Metalloproteinase 2; D020741:rho GTP-Binding Proteins