| First Author | Chien CH | Year | 2015 |
| Journal | PLoS One | Volume | 10 |
| Issue | 2 | Pages | e0115827 |
| PubMed ID | 25706411 | Mgi Jnum | J:226303 |
| Mgi Id | MGI:5696725 | Doi | 10.1371/journal.pone.0115827 |
| Citation | Chien CH, et al. (2015) Local immunosuppressive microenvironment enhances migration of melanoma cells to lungs in DJ-1 knockout mice. PLoS One 10(2):e0115827 |
| abstractText | DJ-1 is an oncoprotein that promotes survival of cancer cells through anti-apoptosis. However, DJ-1 also plays a role in regulating IL-1beta expression, and whether inflammatory microenvironment built by dysregulated DJ-1 affects cancer progression is still unclear. This study thus aimed to compare the metastatic abilities of melanoma cells in wild-type (WT) and DJ-1 knockout (KO) mice, and to check whether inflammatory microenvironment built in DJ-1 KO mice plays a role in migration of cancer cells to lungs. First, B16F10 melanoma cells (at 6 x 10(4)) were injected into the femoral vein of mice, and formation of lung nodules, levels of lung IL-1beta and serum cytokines, and accumulation of myeloid-derived suppressor cells (MDSCs) were compared between WT and DJ-1 KO mice. Second, the cancer-bearing mice were treated with an interleukin-1 beta (IL-1beta) neutralizing antibody to see whether IL-1beta is involved in the cancer migration. Finally, cultured RAW 264.7 macrophage and B16F10 melanoma cells were respectively treated with DJ-1 shRNA and recombinant IL-1beta to explore underlying molecular mechanisms. Our results showed that IL-1beta enhanced survival and colony formation of cultured melanoma cells, and that IL-1beta levels were elevated both in DJ-1 KO mice and in cultured macrophage cells with DJ-1 knockdown. The elevated IL-1beta correlated with higher accumulation of immunosuppressive MDSCs and formation of melanoma module in the lung of DJ-1 KO mice, and both can be decreased by treating mice with IL-1beta neutralizing antibodies. Taken together, these results indicate that immunosuppressive tissue microenvironment built in DJ-1 KO mice can enhance lung migration of cancer, and IL-1beta plays an important role in promoting the cancer migration. |
