Details

Autor(en) / Beteiligte

• Romo, Ana
• Rodríguez, Tania Melina
• Yu, Guo
• Dewey, Ricardo Alfredo

Titel

Chimeric TβRII-SE/Fc overexpression by a lentiviral vector exerts strong antitumoral activity on colorectal cancer-derived cell lines in vitro and on xenografts

Ist Teil von

• Cancer gene therapy, 2024-01, Vol.31 (1), p.174-185

Ort / Verlag

New York: Nature Publishing Group US

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• The TGF signaling pathway is a key regulator of cancer progression. In this work, we report for the first time the antitumor activity of TβRII-SE/Fc, a novel peptibody whose targeting domain is comprised of the soluble endogenous isoform of the human TGF-β type II receptor (TβRII-SE). Overexpression of TβRIISE/Fc reduces in vitro cell proliferation and migration while inducing cell cycle arrest and apoptosis in human colorectal cancer-derived cell lines. Moreover, TβRII-SE/Fc overexpression reduces tumorigenicity in BALB/c nude athymic mice. Our results revealed that TRII-SE/Fc-expressing tumors were significantly reduced in size or were even incapable of developing. We also demonstrated that the novel peptibody has the ability to inhibit the canonical TGF-β and BMP signaling pathways while identifying SMAD-dependent and independent proteins involved in tumor progression that are modulated by TβRII-SE/Fc. These findings provide insights into the underlying mechanism responsible for the antitumor activity of TβRII-SE/Fc. Although more studies are required to demonstrate the effectiveness and safety of the novel peptibody as a new therapeutic for the treatment of cancer, our initial in vitro and in vivo results in human colorectal tumor-derived cell lines are highly encouraging. Our results may serve as the foundation for further research and development of a novel biopharmaceutical for oncology.