PLoS ONE (Jan 2013)

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.

  • Francesco Dituri,
  • Antonio Mazzocca,
  • Joan Fernando,
  • Fernando Juan Peidrò,
  • Patrizia Papappicco,
  • Isabel Fabregat,
  • Flavia De Santis,
  • Angelo Paradiso,
  • Carlo Sabbà,
  • Gianluigi Giannelli

DOI
https://doi.org/10.1371/journal.pone.0067109
Journal volume & issue
Vol. 8, no. 6
p. e67109

Abstract

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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.