Resumen:
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.
