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, Fernando Juan Peidrò, Patrizia Papappicco, Isabel Fabregat, Flavia De Santis, Angelo Paradiso, Carlo Sabbà, Gianluigi Giannelli

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article numbere67109
JournalPLoS One
Volume8
Issue number6
DOIs
Publication statusPublished - Jun 27 2013

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LY-2157299
Vitronectin
Antibodies, Monoclonal, Humanized
Phosphorylation
laminin
fibronectins
fibrinogen
Cell growth
neutralizing antibodies
Fibronectins
cell movement
Fibrinogen
collagen
cell growth
clinical trials
monoclonal antibodies
phosphorylation
Collagen
Monoclonal Antibodies
Cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

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; Mazzocca, Antonio; Peidrò, Fernando Juan; Papappicco, Patrizia; Fabregat, Isabel; De Santis, Flavia; Paradiso, Angelo; Sabbà, Carlo; Giannelli, Gianluigi.

In: PLoS One, Vol. 8, No. 6, e67109, 27.06.2013.

Research output: Contribution to journalArticle

Dituri, Francesco ; Mazzocca, Antonio ; Peidrò, Fernando Juan ; Papappicco, Patrizia ; Fabregat, Isabel ; De Santis, Flavia ; Paradiso, Angelo ; Sabbà, Carlo ; Giannelli, Gianluigi. / 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. In: PLoS One. 2013 ; Vol. 8, No. 6.
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