2026-04-14T04:57:16Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/2222502025-12-10T00:48:53Zcom_2072_1057col_2072_478916col_2072_478917

00925njm 22002777a 4500 dc Pizzuto, Elena author Mancarella, Serena author Gigante, Isabella author Serino, Grazia author Dituri, Francesco author Piccinno, Emanuele author Fabregat, Isabel author Giannelli, Gianluigi author 2025-07-15T08:36:47Z 2025-07-15T08:36:47Z 2025-05-22 2025-07-10T14:49:45Z Molecular mechanisms responsible for the poor prognosis in patients with intrahepatic cholangiocarcinoma (CCA) are still unknown, but stem cell marker Cluster Differentiation 90 (CD90) has been reported to be associated with a more aggressive cancer phenotype. In this scenario, the TGF-beta 1 signaling pathway likely has a role as master gene regulator. Aim of the study is to investigate the role of CD90 in iCCA aggressiveness. The molecular profile of HuCCT1/CD90+ and HuCCT1/CD90- cells was obtained through transcriptomic analysis (NGS). Bioinformatic data were confirmed in both cell lines by qRT-PCR and Western blot. Cells were treated with Gemcitabine in monotherapy or in combination with Galunisertib, a selective inhibitor of TGF-beta RI, in 2D and 3D models. HuCCT1/CD90+ cells are more proliferative, less migratory, and resistant to Gemcitabine treatment. HuCCT1/CD90+ cells also express lower levels of TGF-beta 1 compared to /CD90- cell lines. Finally, HuCCT1/CD90+ cells are resistant to Gemcitabine, while the combination of Gemcitabine and Galunisertib displays a synergistic effect on HuCCT1/CD90+ cell proliferation. These results underline that CD90-induced Gemcitabine resistance can be overcome by adding a TGF beta 1 inhibitor such as Galunisertib, thereby moving further toward a precision medicine approach in patients with iCCA. Càncer de fetge Oncogens Liver cancer Oncogenes Inhibiting the TGF-β1 Pathway Reduces the Aggressiveness of Intrahepatic CCA HuCCT1 CD90-Positive Cells