title: Hypoxia suppresses the production of matrix metalloproteinases and the migration of human monocyte-derived dendritic cells.
abstract: As most solid tumors are hypoxic, dendritic cells (DC) in solid tumors are also exposed to hypoxia. While many adaptation responses of tumor cells to hypoxia are known, it is yet to be determined how hypoxia affects the functions of DC. To explore the effects of hypoxia on the functions of DC, we compared the expression of surface markers, cytokines, chemokine receptors and matrix metalloproteinases (MMP) of human monocyte-derived DC (hmDC) differentiated under hypoxia to those differentiated under normoxia. Both groups of hmDC expressed similar levels of surface markers and cytokines. However, expression of MMP-9 and membrane type-1-MMP, as well as migrating activity, was significantly suppressed in hmDC differentiated under hypoxia compared with their normoxia counterparts. We also demonstrated that trichostatin A restored the production of MMP-9 in hmDC, under hypoxia. Collectively, our findings show that a hypoxic microenvironment suppresses the production of MMP in hmDC, most probably through the deacetylation of promoter regions of MMP, thus suppressing the migrating activity of hmDC. Our results suggest that the hypoxic microenvironment in solid tumor tissues may suppress the function of DC.
authors.affiliation: Department of Pathological Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Wenli
authors.initials: W
authors.lastname: Zhao
authors.forename: Stephanie
authors.initials: S
authors.lastname: Darmanin
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Hongyan
authors.initials: H
authors.lastname: Cui
authors.forename: Jingxin
authors.initials: J
authors.lastname: Wang
authors.forename: Futoshi
authors.initials: F
authors.lastname: Okada
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Hamada
authors.forename: Yuu-ichi
authors.initials: Y
authors.lastname: Hattori
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kondo
authors.forename: Junji
authors.initials: J
authors.lastname: Hamuro
authors.forename: Masahiro
authors.initials: M
authors.lastname: Asaka
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D015415:Biomarkers; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000201:enzymology*; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D009000:Monocytes / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000502:physiology
chemical_list: D015415:Biomarkers; D061965:Matrix Metalloproteinase Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1