| First Author | Leal AS | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 7072 |
| PubMed ID | 31068602 | Mgi Jnum | J:279841 |
| Mgi Id | MGI:6357455 | Doi | 10.1038/s41598-019-43430-0 |
| Citation | Leal AS, et al. (2019) The Rho/MRTF pathway inhibitor CCG-222740 reduces stellate cell activation and modulates immune cell populations in Kras(G12D); Pdx1-Cre (KC) mice. Sci Rep 9(1):7072 |
| abstractText | The stromal reaction in pancreatic cancer creates a physical barrier that blocks therapeutic intervention and creates an immunosuppressive tumor microenvironment. The Rho/myocardin-related transcription factor (MRTF) pathway is implicated in the hyper-activation of fibroblasts in fibrotic diseases and the activation of pancreatic stellate cells. In this study we use CCG-222740, a small molecule, designed as a Rho/MRTF pathway inhibitor. This compound decreases the activation of stellate cells in vitro and in vivo, by reducing the levels of alpha smooth muscle actin (alpha-SMA) expression. CCG-222740 also modulates inflammatory components of the pancreas in KC mice (LSL-Kras(G12D/+); Pdx-1-Cre) stimulated with caerulein. It decreases the infiltration of macrophages and increases CD4 T cells and B cells. Analysis of the pancreatic adenocarcinoma (PDA) TCGA dataset revealed a correlation between elevated RhoA, RhoC and MRTF expression and decreased survival in PDA patients. Moreover, a MRTF signature is correlated with a Th2 cell signature in human PDA tumors. |
