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

While molecular subgrouping has revolutionized medulloblastoma classification, the extent of heterogeneity within subgroups is unknown. Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes. After integration of somatic copy-number alterations, and clinical features specific to each cluster, we identify 12 different subtypes of medulloblastoma. Integrative analysis using SNF further delineates group 3 from group 4 medulloblastoma, which is not as readily apparent through analyses of individual data types. Two clear subtypes of infants with Sonic Hedgehog medulloblastoma with disparate outcomes and biology are identified. Medulloblastoma subtypes identified through integrative clustering have important implications for stratification of future clinical trials.

• MeSH
• genomika MeSH
• individualizovaná medicína * MeSH
• kohortové studie MeSH
• lidé MeSH
• meduloblastom klasifikace   genetika   terapie   MeSH
• metylace DNA MeSH
• shluková analýza MeSH
• stanovení celkové genové exprese MeSH
• variabilita počtu kopií segmentů DNA MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH