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Differential Inhibition of the TGF-? Signaling Pathway in HCC Cells Using the Small Molecule Inhibitor LY2157299 and the D10 Monoclonal Antibody against TGF-? Receptor Type II.


ABSTRACT: We investigated blocking the TGF-? signaling pathway in HCC using two small molecule inhibitors (LY2157299, LY2109761) and a neutralizing humanized antibody (D10) against TGF-?RII. 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-?RII. 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-? receptor cycling in cancer cells.

SUBMITTER: Dituri F 

PROVIDER: S-EPMC3694933 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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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 Francesco F   Mazzocca Antonio A   Fernando Joan J   Peidrò Fernando Juan FJ   Papappicco Patrizia P   Fabregat Isabel I   De Santis Flavia F   Paradiso Angelo A   Sabbà Carlo C   Giannelli Gianluigi G  

PloS one 20130627 6


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  ...[more]

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