TLR4 Signaling Induces the Release of Microparticles by Tumor Cells That Regulate Inflammatory Cytokine IL-6 of Macrophages Via MicroRNA Let-7b

Overview

Journal Oncoimmunology

Specialty Allergy & Immunology

Date 2012 Aug 31

PMID 22934260

Citations 25

Authors

Dapeng Li

Haibo Jia

Huafeng Zhang

Meng Lv

Jing Liu

Yi Zhang

Tao Huang

Bo Huang

Affiliations

Soon will be listed here.

Abstract

Tumor cells expressing TLRs is generally recognized to mediate tumor inflammation. However, whether and how tumor TLR signaling pathways negatively regulate tumor inflammation remains unclear. In this report, we find that TLR4 signaling of H22 hepatocarcinoma tumor cells is transduced through MyD88 pathway to actin cytoskeletons, leading to the release of microparticles (MPs), the cellular membrane-derived vesicles. As a result, tumor macrophages take up MPs and acquire MP-contained microRNA let-7b, which attenuates tumor inflammation by targeting proinflammatory cytokine IL-6. Thus, tumor TLR signaling, contrary to the original promoting effect, may play an opposite role in downregulating tumor inflammation through MP pathways.

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References

Iliopoulos D, Hirsch H, Struhl K . An epigenetic switch involving NF-kappaB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation. Cell. 2009; 139(4):693-706. PMC: 2783826. DOI: 10.1016/j.cell.2009.10.014. View

Loffler D, Brocke-Heidrich K, Pfeifer G, Stocsits C, Hackermuller J, Kretzschmar A . Interleukin-6 dependent survival of multiple myeloma cells involves the Stat3-mediated induction of microRNA-21 through a highly conserved enhancer. Blood. 2007; 110(4):1330-3. DOI: 10.1182/blood-2007-03-081133. View

Tang K, Liu J, Yang Z, Zhang B, Zhang H, Huang C . Microparticles mediate enzyme transfer from platelets to mast cells: a new pathway for lipoxin A4 biosynthesis. Biochem Biophys Res Commun. 2010; 400(3):432-6. DOI: 10.1016/j.bbrc.2010.08.095. View

DeNardo D, Johansson M, Coussens L . Immune cells as mediators of solid tumor metastasis. Cancer Metastasis Rev. 2007; 27(1):11-8. DOI: 10.1007/s10555-007-9100-0. View

Solinas G, Germano G, Mantovani A, Allavena P . Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. J Leukoc Biol. 2009; 86(5):1065-73. DOI: 10.1189/jlb.0609385. View

Nelson D, Ganss R . Tumor growth or regression: powered by inflammation. J Leukoc Biol. 2006; 80(4):685-90. DOI: 10.1189/jlb.1105646. View

Davidson-Moncada J, Papavasiliou F, Tam W . MicroRNAs of the immune system: roles in inflammation and cancer. Ann N Y Acad Sci. 2010; 1183:183-94. PMC: 2876712. DOI: 10.1111/j.1749-6632.2009.05121.x. View

Huang B, Zhao J, Shen S, Li H, He K, Shen G . Listeria monocytogenes promotes tumor growth via tumor cell toll-like receptor 2 signaling. Cancer Res. 2007; 67(9):4346-52. DOI: 10.1158/0008-5472.CAN-06-4067. View

Thery C, Ostrowski M, Segura E . Membrane vesicles as conveyors of immune responses. Nat Rev Immunol. 2009; 9(8):581-93. DOI: 10.1038/nri2567. View

10.

Sims G, Rowe D, Rietdijk S, Herbst R, Coyle A . HMGB1 and RAGE in inflammation and cancer. Annu Rev Immunol. 2010; 28:367-88. DOI: 10.1146/annurev.immunol.021908.132603. View

11.

Grivennikov S, Greten F, Karin M . Immunity, inflammation, and cancer. Cell. 2010; 140(6):883-99. PMC: 2866629. DOI: 10.1016/j.cell.2010.01.025. View

12.

Mack M, Kleinschmidt A, Bruhl H, Klier C, Nelson P, Cihak J . Transfer of the chemokine receptor CCR5 between cells by membrane-derived microparticles: a mechanism for cellular human immunodeficiency virus 1 infection. Nat Med. 2000; 6(7):769-75. DOI: 10.1038/77498. View

13.

Nightingale T, White I, Doyle E, Turmaine M, Harrison-Lavoie K, Webb K . Actomyosin II contractility expels von Willebrand factor from Weibel-Palade bodies during exocytosis. J Cell Biol. 2011; 194(4):613-29. PMC: 3160584. DOI: 10.1083/jcb.201011119. View

14.

Schulte L, Eulalio A, Mollenkopf H, Reinhardt R, Vogel J . Analysis of the host microRNA response to Salmonella uncovers the control of major cytokines by the let-7 family. EMBO J. 2011; 30(10):1977-89. PMC: 3098495. DOI: 10.1038/emboj.2011.94. View

15.

Masedunskas A, Sramkova M, Parente L, Sales K, Amornphimoltham P, Bugge T . Role for the actomyosin complex in regulated exocytosis revealed by intravital microscopy. Proc Natl Acad Sci U S A. 2011; 108(33):13552-7. PMC: 3158220. DOI: 10.1073/pnas.1016778108. View

16.

Collino F, Deregibus M, Bruno S, Sterpone L, Aghemo G, Viltono L . Microvesicles derived from adult human bone marrow and tissue specific mesenchymal stem cells shuttle selected pattern of miRNAs. PLoS One. 2010; 5(7):e11803. PMC: 2910725. DOI: 10.1371/journal.pone.0011803. View

17.

Savina A, Furlan M, Vidal M, Colombo M . Exosome release is regulated by a calcium-dependent mechanism in K562 cells. J Biol Chem. 2003; 278(22):20083-90. DOI: 10.1074/jbc.M301642200. View

18.

Huang B, Zhao J, Li H, He K, Chen Y, Chen S . Toll-like receptors on tumor cells facilitate evasion of immune surveillance. Cancer Res. 2005; 65(12):5009-14. DOI: 10.1158/0008-5472.CAN-05-0784. View

19.

Morel O, Toti F, Hugel B, Freyssinet J . Cellular microparticles: a disseminated storage pool of bioactive vascular effectors. Curr Opin Hematol. 2004; 11(3):156-64. DOI: 10.1097/01.moh.0000131441.10020.87. View

20.

Yuan A, Farber E, Rapoport A, Tejada D, Deniskin R, Akhmedov N . Transfer of microRNAs by embryonic stem cell microvesicles. PLoS One. 2009; 4(3):e4722. PMC: 2648987. DOI: 10.1371/journal.pone.0004722. View