Reference - Detail
| RRC ID | 62928 |
|---|---|
| Author | Takahashi K, Akatsu Y, Podyma-Inoue KA, Matsumoto T, Takahashi H, Yoshimatsu Y, Koinuma D, Shirouzu M, Miyazono K, Watabe T. |
| Title | Targeting all transforming growth factor-β isoforms with an Fc chimeric receptor impairs tumor growth and angiogenesis of oral squamous cell cancer. |
| Journal | J Biol Chem |
| Abstract |
Tumor progression is governed by various growth factors and cytokines in the tumor microenvironment (TME). Among these, transforming growth factor-β (TGF-β) is secreted by various cell types residing in the TME and promotes tumor progression by inducing the epithelial-to-mesenchymal transition (EMT) of cancer cells and tumor angiogenesis. TGF-β comprises three isoforms, TGF-β1, -β2, and -β3, and transduces intracellular signals via TGF-β type I receptor (TβRI) and TGF-β type II receptor (TβRII). For the purpose of designing ligand traps that reduce oncogenic signaling in the TME, chimeric proteins comprising the ligand-interacting ectodomains of receptors fused with the Fc portion of immunoglobulin are often used. For example, chimeric soluble TβRII (TβRII-Fc) has been developed as an effective therapeutic strategy for targeting TGF-β ligands, but several lines of evidence indicate that TβRII-Fc more effectively traps TGF-β1 and TGF-β3 than TGF-β2, whose expression is elevated in multiple cancer types. In the present study, we developed a chimeric TGF-β receptor containing both TβRI and TβRII (TβRI-TβRII-Fc) and found that TβRI-TβRII-Fc trapped all TGF-β isoforms, leading to inhibition of both the TGF-β signal and TGF-β-induced EMT of oral cancer cells, whereas TβRII-Fc failed to trap TGF-β2. Furthermore, we found that TβRI-TβRII-Fc suppresses tumor growth and angiogenesis more effectively than TβRII-Fc in a subcutaneous xenograft model of oral cancer cells with high TGF-β expression. These results suggest that TβRI-TβRII-Fc may be a promising tool for targeting all TGF-β isoforms in the TME. |
| Volume | 295(36) |
| Pages | 12559-12572 |
| Published | 2020-9-4 |
| DOI | 10.1074/jbc.RA120.012492 |
| PII | S0021-9258(17)49974-1 |
| PMID | 32631954 |
| PMC | PMC7476713 |
| MeSH | Animals Antineoplastic Agents / therapeutic use* Carcinoma, Squamous Cell / drug therapy* Carcinoma, Squamous Cell / metabolism HEK293 Cells Humans Male Mice Mice, Inbred BALB C Mice, Nude Mouth Neoplasms / drug therapy* Mouth Neoplasms / metabolism Neovascularization, Pathologic / drug therapy* Protein Isoforms / antagonists & inhibitors Protein Isoforms / metabolism Receptors, Fc / genetics* Receptors, Fc / metabolism Receptors, Transforming Growth Factor beta / genetics Receptors, Transforming Growth Factor beta / metabolism* Recombinant Proteins / genetics Recombinant Proteins / metabolism Recombinant Proteins / therapeutic use Transforming Growth Factor beta / antagonists & inhibitors* Transforming Growth Factor beta / metabolism Tumor Microenvironment |
| IF | 4.238 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 16 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | SAS(RCB1974) |