The aim of this study was to analyze the potential role of NG2 chondroitin sulfate proteoglycan in amoeboid morphology and invasiveness of cancer cells. In the highly metastatic amoeboid cell lines A3 and A375M2, siRNA-mediated down-regulation of NG2 induced an amoeboid-mesenchymal transition associated with decreased invasiveness in 3D collagen and inactivation of the GTPase Rho. Conversely, the expression of NG2 in mesenchymal sarcoma K2 cells as well as in A375M2 cells resulted in an enhanced amoeboid phenotype associated with increased invasiveness and elevated Rho-GTP levels. Remarkably, the amoeboid-mesenchymal transition in A375M2 cells triggered by NG2 down-regulation was associated with increased extracellular matrix-degrading ability, although this was not sufficient to compensate for the decreased invasive capability caused by down-regulated Rho/ROCK signaling. Conversely, in K2 cells with overexpression of NG2, the ability to degrade the extracellular matrix was greatly reduced. Taken together, we suggest that NG2-mediated activation of Rho leading to effective amoeboid invasiveness is a possible mechanism through which NG2 could contribute to tumor cell invasion and metastasis.
- MeSH
- chondroitinsulfát proteoglykany genetika metabolismus MeSH
- down regulace MeSH
- extracelulární matrix metabolismus MeSH
- invazivní růst nádoru MeSH
- kinázy asociované s rho metabolismus MeSH
- kolagen chemie MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- malá interferující RNA MeSH
- membránové proteiny genetika metabolismus MeSH
- molekulární konformace MeSH
- nádorové buněčné linie MeSH
- nádory metabolismus patologie ultrastruktura MeSH
- pohyb buněk * MeSH
- rho proteiny vázající GTP metabolismus MeSH
- upregulace MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
