Reference SummaryVernon PJ, J Immunol 2013 Feb 1;190(3):1372-9
Title |
The receptor for advanced glycation end products promotes pancreatic carcinogenesis and accumulation of myeloid-derived suppressor cells. |
Authors |
Vernon PJ; Loux TJ; Schapiro NE; Kang R; Muthuswamy R; Kalinski P; Tang D; Lotze MT; Zeh HJ 3rd |
Journal |
J Immunol |
Volume |
190 |
Issue |
3 |
Year |
2013 |
Pages |
1372-9 |
Abstract |
Pancreatic ductal adenocarcinoma (PDA) has an aggressive natural history and is resistant to therapy. The receptor for advanced glycation end products (RAGE) is a pattern recognition receptor for many damage-associated molecular pattern molecules. RAGE is overexpressed in both human and murine models of PDA as well as most advanced epithelial neoplasms. The immunosuppressive nature of the PDA microenvironment is facilitated, in part, by the accumulation of regulatory immune cell infiltrates such as myeloid-derived suppressor cells (MDSCs). To study the role of RAGE expression in the setting of mutant Ras-promoted pancreatic carcinogenesis (KC), a triple-transgenic model of spontaneous murine PDA in a RAGE-null background (KCR) was generated. KCR mice had markedly delayed pancreatic carcinogenesis and a significant diminution of MDSCs compared with KC mice at comparable time points postweaning. Although RAGE was not required for the development or suppressor activity of MDSCs, its absence was associated with temporally limited pancreatic neoplasia and altered phenotype and function of the myeloid cells. In lieu of MDSCs, KCR animals at comparable time points exhibited mature CD11b(+)Gr1(-)F4/80(+) cells that were not immunosuppressive in vitro. KCR mice also maintained a significantly less suppressive milieu evidenced by marked decreases in CCL22 in relation to CXCL10 and diminished serum levels of IL-6. |
Links |
J:192593 – MGI References 23269246 – National Library of Medicine/PubMed |
| Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
|---|---|---|---|---|---|
| B6;129S-Agertm1.1Arnd Krastm4Tyj/+ Tg(Pdx1-cre)6Tuv | Pancreas - Duct atypia | Pancreas - Duct |
observed |
||
| C57BL/6-Krastm4Tyj/+ Tg(Pdx1-cre)6Tuv | Pancreas - Duct atypia | Pancreas - Duct |
observed |
||
| B6;129S-Agertm1.1Arnd Krastm4Tyj/+ Tg(Pdx1-cre)6Tuv | Pancreas - Duct dysplasia | Pancreas - Duct |
observed |
||
| C57BL/6-Krastm4Tyj/+ Tg(Pdx1-cre)6Tuv | Pancreas - Duct dysplasia | Pancreas - Duct |
observed |
||
| B6;129S-Agertm1.1Arnd Krastm4Tyj/+ Tg(Pdx1-cre)6Tuv | Pancreas - Duct hyperplasia - epithelial | Pancreas - Duct |
observed |
||
| C57BL/6-Krastm4Tyj/+ Tg(Pdx1-cre)6Tuv | Pancreas - Duct hyperplasia - epithelial | Pancreas - Duct |
observed |
||
| C57BL/6NTac | Pancreas pancreatic intraepithelial neoplasia (PanIN) | Pancreas |
0 |
||
| B6;129S-Agertm1.1Arnd | Pancreas pancreatic intraepithelial neoplasia (PanIN) | Pancreas |
0 |
||
| B6;129S-Agertm1.1Arnd Krastm4Tyj/+ Tg(Pdx1-cre)6Tuv | Pancreas pancreatic intraepithelial neoplasia (PanIN) | Pancreas |
0 |
||
| C57BL/6-Krastm4Tyj/+ Tg(Pdx1-cre)6Tuv | Pancreas pancreatic intraepithelial neoplasia (PanIN) - high grade | Pancreas |
observed |
||
| C57BL/6-Krastm4Tyj/+ Tg(Pdx1-cre)6Tuv | Pancreas pancreatic intraepithelial neoplasia (PanIN) - low grade | Pancreas |
observed |
||
| C57BL/6-Krastm4Tyj/+ Tg(Pdx1-cre)6Tuv | Pancreas preneoplastic lesion | Pancreas |
observed |