Differential Inhibition of the TGF-β Signaling Pathway in HCC Cells Using the Small Molecule Inhibitor LY2157299 and the D10 Monoclonal Antibody against TGF-β Receptor Type II.
- Dituri F
- MAZZOCCA, ANTONIO
- Peidrò FJ
- Papappicco P
- Fabregat I
- De Santis F
- Paradiso A
- SABBA', Carlo
- GIANNELLI, Gianluigi
Publication date
January 2013
DOI Publisher
Public Library of Science (PLoS) ISSN
1932-6203 Citation count (estimate)
42Abstract
We investigated blocking the TGF-β signaling pathway in HCC using two small molecule inhibitors (LY2157299, LY2109761) and a neutralizing humanized antibody (D10) against TGF-βRII. LY2157299 and LY2109761 inhibited HCC cell migration on Laminin-5, Fibronectin, Vitronectin, Fibrinogen and Collagen-I and de novo phosphorylation of pSMAD2. LY2157299 inhibited HCC migration and cell growth independently of the expression levels of TGF-βRII. In contrast to LY2157299, D10 showed a reduction in pSMAD2 only after a short exposure. This study supports the use of LY2157299 in clinical trials, and presents new insights into TGF-β receptor cycling in cancer cells