title: Local immunosuppressive microenvironment enhances migration of melanoma cells to lungs in DJ-1 knockout mice.
abstract: DJ-1 is an oncoprotein that promotes survival of cancer cells through anti-apoptosis. However, DJ-1 also plays a role in regulating IL-1β 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-1β 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-1β) neutralizing antibody to see whether IL-1β 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-1β to explore underlying molecular mechanisms. Our results showed that IL-1β enhanced survival and colony formation of cultured melanoma cells, and that IL-1β levels were elevated both in DJ-1 KO mice and in cultured macrophage cells with DJ-1 knockdown. The elevated IL-1β 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-1β 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-1β plays an important role in promoting the cancer migration.
authors.affiliation: Department of Life Science, College of Life Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Chien
authors.affiliation: Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Ming-Jen
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Houng-Chi
authors.initials: HC
authors.lastname: Liou
authors.affiliation: Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan; Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Horng-Huei
authors.initials: HH
authors.lastname: Liou
authors.affiliation: Department of Life Science, College of Life Science, National Taiwan University, Taipei, Taiwan; Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Wen-Mei
authors.initials: WM
authors.lastname: Fu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D060833:Cellular Microenvironment / Q000276:immunology*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology* / Q000556:secondary; D008214:Lymphocytes / Q000276:immunology; D008545:Melanoma / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000276:immunology / Q000502:physiology; D009361:Neoplasm Invasiveness; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism*; D000071617:Protein Deglycase DJ-1
chemical_list: D053583:Interleukin-1beta; D015513:Oncogene Proteins; D054464:Peroxiredoxins; C503466:PARK7 protein, mouse; D000071617:Protein Deglycase DJ-1