| First Author | Loftus PG | Year | 2021 |
| Journal | Int J Cancer | Volume | 148 |
| Issue | 5 | Pages | 1245-1259 |
| PubMed ID | 33152121 | Mgi Jnum | J:301562 |
| Mgi Id | MGI:6505639 | Doi | 10.1002/ijc.33383 |
| Citation | Loftus PG, et al. (2021) Targeting stromal cell Syndecan-2 reduces breast tumour growth, metastasis and limits immune evasion. Int J Cancer 148(5):1245-1259 |
| abstractText | Tumour stromal cells support tumourigenesis. We report that Syndecan-2 (SDC2) is expressed on a nonepithelial, nonhaematopoietic, nonendothelial stromal cell population within breast cancer tissue. In vitro, syndecan-2 modulated TGFbeta signalling (SMAD7, PAI-1), migration and immunosuppression of patient-derived tumour-associated stromal cells (TASCs). In an orthotopic immunocompromised breast cancer model, overexpression of syndecan-2 in TASCs significantly enhanced TGFbeta signalling (SMAD7, PAI-1), tumour growth and metastasis, whereas reducing levels of SDC2 in TASCs attenuated TGFbeta signalling (SMAD7, PAI-1, CXCR4), tumour growth and metastasis. To explore the potential for therapeutic application, a syndecan-2-peptide was generated that inhibited the migratory and immunosuppressive properties of TASCs in association with reduced expression of TGFbeta-regulated immunosuppressive genes, such as CXCR4 and PD-L1. Moreover, using an orthotopic syngeneic breast cancer model, overexpression of syndecan-2-peptide in TASCs reduced tumour growth and immunosuppression within the TME. These data provide evidence that targeting stromal syndecan-2 within the TME inhibits tumour growth and metastasis due to decreased TGFbeta signalling and increased immune control. |
