title: 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.
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.
authors.affiliation: Department of Emergency and Organ Transplantation, Section of Internal Medicine Allergology and Immunology, University of Bari Medical School, Bari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Dituri
authors.forename: Antonio
authors.initials: A
authors.lastname: Mazzocca
authors.forename: Joan
authors.initials: J
authors.lastname: Fernando
authors.forename: Fernando Juan
authors.initials: FJ
authors.lastname: Peidrò
authors.forename: Patrizia
authors.initials: P
authors.lastname: Papappicco
authors.forename: Isabel
authors.initials: I
authors.lastname: Fabregat
authors.forename: Flavia
authors.initials: F
authors.lastname: De Santis
authors.forename: Angelo
authors.initials: A
authors.lastname: Paradiso
authors.forename: Carlo
authors.initials: C
authors.lastname: Sabbà
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Giannelli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D005260:Female; D056945:Hep G2 Cells; D018398:Homeodomain Proteins / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000378:metabolism; D014157:Transcription Factors / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C526317:CCN2 protein, human; D018398:Homeodomain Proteins; C530108:LY2109761; D011720:Pyrazoles; D011758:Pyrroles; D011804:Quinolines; D018125:Receptors, Transforming Growth Factor beta; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D055513:Connective Tissue Growth Factor; C072064:HOXD10 protein, human; C557799:LY-2157299; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II