biostudies-literatureUnknown10(2)Chien CHDJ-1 is an oncoprotein that promotes survival of cancer cells through anti-apoptosis. However, DJ-1 also plays a role in regulating IL-1? 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 × 10(4)) were injected into the femoral vein of mice, and formation of lung nodules, levels of lung IL-1? 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-1?) neutralizing antibody to see whether IL-1? 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-1? to explore underlying molecular mechanisms. Our results showed that IL-1? enhanced survival and colony formation of cultured melanoma cells, and that IL-1? levels were elevated both in DJ-1 KO mice and in cultured macrophage cells with DJ-1 knockdown. The elevated IL-1? 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-1? 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-1? plays an important role in promoting the cancer migration.PloS onee0115827https://www.ebi.ac.uk/biostudies/studies/S-EPMC4338246biostudies-literatureLocal immunosuppressive microenvironment enhances migration of melanoma cells to lungs in DJ-1 knockout mice.PMC4338246Liou HCLiou HHFu WMChien CHLee MJfalseLocal immunosuppressive microenvironment enhances migration of melanoma cells to lungs in DJ-1 knockout mice.DJ-1 is an oncoprotein that promotes survival of cancer cells through anti-apoptosis. However, DJ-1 also plays a role in regulating IL-1? 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 × 10(4)) were injected into the femoral vein of mice, and formation of lung nodules, levels of lung IL-1? 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-1?) neutralizing antibody to see whether IL-1? 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-1? to explore underlying molecular mechanisms. Our results showed that IL-1? enhanced survival and colony formation of cultured melanoma cells, and that IL-1? levels were elevated both in DJ-1 KO mice and in cultured macrophage cells with DJ-1 knockdown. The elevated IL-1? 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-1? 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-1? plays an important role in promoting the cancer migration.2015-01-01T00:00:00Z20152021-02-20T21:07:51Z2019-03-26T23:30:24ZS-EPMC43382462570641110.1371/journal.pone.0115827