Histone Deacetylase-3 Mediates Positive Feedback Relationship between Anaphylaxis and Tumor Metastasis
Histone Deacetylase-3 Mediates Positive Feedback Relationship between Anaphylaxis and Tumor Metastasis
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DOI：
10.1074/jbc.m113.521245
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发表时间：
2014-04-25
影响因子：
4.8
通讯作者：
Jeoung, Dooil
中科院分区：
文献类型：
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作者：
Eom, Sangkyung;Kim, Youngmi;Jeoung, Dooil
背景：过敏反应和肿瘤转移之间的关系在分子水平上仍不清楚。结果：miR-384/HDAC 3轴调控肿瘤细胞和肥大细胞之间的相互作用。结论：HDAC 3在过敏反应和肿瘤转移之间介导正反馈回路。重要性：HDAC 3可以作为过敏和癌症治疗的靶点，过敏性炎症可以增强肿瘤细胞的转移潜能。报道了组蛋白去乙酰化酶3（HDAC 3）在过敏性皮肤炎症中的作用。我们研究了HDAC 3参与过敏性炎症-促进肿瘤细胞的转移潜力。被动全身过敏反应（PSA）诱导BALB/c小鼠HDAC 3表达和FcERI信号转导。PSA以HDAC 3和单核细胞趋化蛋白1（MCP 1）依赖的方式增强小鼠黑色素瘤细胞的致瘤性和转移潜能。PSA介导的转移潜能增强涉及诱导肺肿瘤组织中HDAC 3、MCP 1和CD 11b（巨噬细胞标志物）的表达。我们在分子水平上研究了过敏反应与肿瘤生长和转移之间的相互作用。来自抗原刺激的骨髓来源的小鼠肥大细胞培养物的条件培养基诱导B16 F1小鼠黑色素瘤细胞中HDAC 3、MCP 1和MCP 1受体CCR 2的表达，并增强B16 F1细胞的迁移和侵袭潜力。来自B16 F10培养物的条件培养基以HDAC 3依赖性方式诱导肺肥大细胞中FcERI信号传导的活化。在源自B16 F10细胞的肺肿瘤中观察到FcERI信号传导。靶点扫描分析预测HDAC 3是miR-384的靶点，发现miR-384与HDAC 3形成反馈调节环。miR-384通过PSA降低，负调节HDAC 3表达、过敏性炎症以及过敏反应和肿瘤转移之间的正反馈调节环。我们发现miR-384/HDAC 3反馈环是过敏反应和肿瘤转移之间正反馈关系的新调节因子。
Background: The relationship between anaphylaxis and tumor metastasis remains unknown at the molecular level. Results: The miR-384/HDAC3 axis regulates an interaction between tumor cells and mast cells. Conclusion: HDAC3 mediates a positive feedback loop between anaphylaxis and tumor metastasis. Significance: HDAC3 can be a target for the development of allergy and cancer therapeutics.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 FcERI 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 FcERI signaling in lung mast cells in an HDAC3-dependent manner. FcERI 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.