title: Histone deacetylase-3 mediates positive feedback relationship between anaphylaxis and tumor metastasis.
abstract: Allergic inflammation has been known to enhance the metastatic potential of tumor cells. The role of histone deacetylase-3 (HDAC3) in allergic skin inflammation was reported. We investigated HDAC3 involvement in the allergic inflammation-promotion of metastatic potential of tumor cells. Passive systemic anaphylaxis (PSA) induced HDAC3 expression and FcεRI signaling in BALB/c mice. PSA enhanced the tumorigenic and metastatic potential of mouse melanoma cells in HDAC3- and monocyte chemoattractant protein 1-(MCP1)-dependent manner. The PSA-mediated enhancement of metastatic potential involved the induction of HDAC3, MCP1, and CD11b (a macrophage marker) expression in the lung tumor tissues. We examined an interaction between anaphylaxis and tumor growth and metastasis at the molecular level. Conditioned medium from antigen-stimulated bone marrow-derived mouse mast cell cultures induced the expression of HDAC3, MCP1, and CCR2, a receptor for MCP1, in B16F1 mouse melanoma cells and enhanced migration and invasion potential of B16F1 cells. The conditioned medium from B16F10 cultures induced the activation of FcεRI signaling in lung mast cells in an HDAC3-dependent manner. FcεRI signaling was observed in lung tumors derived from B16F10 cells. Target scan analysis predicted HDAC3 to be as a target of miR-384, and miR-384 and HDAC3 were found to form a feedback regulatory loop. miR-384, which is decreased by PSA, negatively regulated HDAC3 expression, allergic inflammation, and the positive feedback regulatory loop between anaphylaxis and tumor metastasis. We show the miR-384/HDAC3 feedback loop to be a novel regulator of the positive feedback relationship between anaphylaxis and tumor metastasis.
authors.affiliation: Departments of Biochemistry, Kangwon National University, Chunchon 200-701.
authors.forename: Sangkyung
authors.initials: S
authors.lastname: Eom
authors.affiliation: Departments of Biochemistry, Kangwon National University, Chunchon 200-701.
authors.forename: Youngmi
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Departments of Biochemistry, Kangwon National University, Chunchon 200-701.
authors.forename: Deokbum
authors.initials: D
authors.lastname: Park
authors.affiliation: Departments of Biological Sciences, College of Natural Sciences, Kangwon National University, Chunchon 200-701.
authors.forename: Hansoo
authors.initials: H
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Yun Sil
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Graduate School of Medicine, Kangwon National University, Chunchon 200-701.
authors.forename: Jongseon
authors.initials: J
authors.lastname: Choe
authors.affiliation: Graduate School of Medicine, Kangwon National University, Chunchon 200-701.
authors.forename: Young Myeong
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Departments of Biochemistry, Kangwon National University, Chunchon 200-701. Electronic address: jeoungd@kangwon.ac.kr.
authors.forename: Dooil
authors.initials: D
authors.lastname: Jeoung
mesh_terms: D000707:Anaphylaxis / Q000201:enzymology* / Q000503:physiopathology; D000818:Animals; D001483:Base Sequence; D001831:Body Temperature; D045744:Cell Line, Tumor; D017931:DNA Primers; D005260:Female; D006655:Histone Deacetylases / Q000378:metabolism*; D008407:Mast Cells / Q000276:immunology; D008546:Melanoma, Experimental / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018945:Monocyte Chemoattractant Proteins / Q000378:metabolism; D009362:Neoplasm Metastasis; D051381:Rats; D000099186:Histone Deacetylase 3
chemical_list: D017931:DNA Primers; D006655:Histone Deacetylases; D018945:Monocyte Chemoattractant Proteins; D000099186:Histone Deacetylase 3
keywords: Allergy; Anaphylaxis; Cell-Cell Interaction; Histone Deacetylase; Histone Deacetylase-3; MicroRNA; MicroRNA-384; Positive Feedback Regulatory Loop; Tumor Metastases