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Hypoxic Lung-Cancer-Derived Extracellular Vesicle MicroRNA-103a Increases the Oncogenic Effects of Macrophages by Targeting PTEN.
Hsu, Ya-Ling; Hung, Jen-Yu; Chang, Wei-An; Jian, Shu-Fang; Lin, Yi-Shiuan; Pan, Yi-Chung; Wu, Cheng-Ying; Kuo, Po-Lin.
Afiliación
  • Hsu YL; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
  • Hung JY; Division of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
  • Chang WA; Division of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
  • Jian SF; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
  • Lin YS; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
  • Pan YC; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
  • Wu CY; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
  • Kuo PL; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Institute of Medical Science and Technology, National Sun Yat-Sen University, K
Mol Ther ; 26(2): 568-581, 2018 02 07.
Article en En | MEDLINE | ID: mdl-29292163
Hypoxia, the most commonly observed characteristic in cancers, is implicated in the establishment of an immunosuppressive niche. Recent studies have indicated that extracellular vesicle (EV)-mediated cancer-stroma interactions are considered to play a critical role in the regulation of various cellular biological functions, with phenotypic consequences in recipient cells. However, the mechanisms underlying the relationship between EVs and hypoxia during cancer progression remain largely unknown. In this study, we found that EVs derived from hypoxic lung cancers increased M2-type polarization by miR-103a transfer. Decreased PTEN levels caused by hypoxic cancer-cell-derived EV miR-103a increased activation of AKT and STAT3 as well as expression of several immunosuppressive and pro-angiogeneic factors. In contrast, inhibition of miR-103a by an miRNA inhibitor effectively decreased hypoxic cancer-mediated M2-type polarization, improving the cytokine prolife of tumor infiltration macrophages. Macrophages received cancer-cell-derived EV miR-103a feedback to further enhance cancer progression and tumor angiogenesis. Finally, circulating EV miR-103a levels were higher in patients with lung cancer and closely associated with the M2 polarization. In conclusion, our results delineate a novel mechanism by which lung cancer cells induce immunosuppressive and pro-tumoral macrophages through EVs and inspire further research into the clinical application of EV inhibition or PTEN restoration for immunotherapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: MicroARNs / Interferencia de ARN / Fosfohidrolasa PTEN / Neoplasias Pulmonares / Macrófagos / Hipoxia Límite: Humans Idioma: En Revista: Mol Ther Asunto de la revista: BIOLOGIA MOLECULAR / TERAPEUTICA Año: 2018 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: MicroARNs / Interferencia de ARN / Fosfohidrolasa PTEN / Neoplasias Pulmonares / Macrófagos / Hipoxia Límite: Humans Idioma: En Revista: Mol Ther Asunto de la revista: BIOLOGIA MOLECULAR / TERAPEUTICA Año: 2018 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos