Down-regulation of IKKβ expression in glioma-infiltrating microglia/macrophages is associated with defective inflammatory/immune gene responses in glioblastoma

Oncotarget

Volumn 6, Issue 32, 2015, Pages 33077-33090

  Mieczkowski, Jakub ^a   Kocyk, Marta ^a,b   Nauman, Pawel ^c   Gabrusiewicz, Konrad ^a   Sielska, Małgorzata ^a   Przanowski, Piotr ^a   Maleszewska, Marta ^a   Rajan, Wenson D ^a   Pszczolkowska, Dominika ^a   Tykocki, Tomasz ^c   Grajkowska, Wieslawa ^d   Kotulska, Katarzyna ^d   Roszkowski, Marcin ^d   Kostkiewicz, Boguslaw ^e   Kaminska, Bozena ^a  

^a NENCKI INSTITUTE OF EXPERIMENTAL BIOLOGY   (Poland)

^b MEDICAL UNIVERSITY OF WARSAW   (Poland)

^c INSTITUTE OF PSYCHIATRY AND NEUROLOGY   (Poland)

^d CHILDREN'S MEMORIAL HEALTH INSTITUTE   (Poland)

^e Clinical Hospital of Interior   (Poland)

Author keywords

Glioblastoma; Glioma associated microglia macrophages; Global gene expression profiling; IKK NFkB signaling; Immunosuppression

Indexed keywords

CD11B ANTIGEN; I KAPPA B KINASE BETA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; I KAPPA B KINASE; IKBKB PROTEIN, HUMAN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CANCER INFILTRATION; CELLULAR DISTRIBUTION; CONTROLLED STUDY; DOWN REGULATION; GENE; GENE EXPRESSION; GENE FUNCTION; GENE ONTOLOGY; GENETIC TRANSCRIPTION; GLIOBLASTOMA; GLIOMA; HUMAN; HUMAN CELL; HUMAN TISSUE; IKBKB GENE; IMMUNE RESPONSE; IMMUNOHISTOCHEMISTRY; IMMUNOREACTIVITY; MACROPHAGE; MALE; MICROGLIA; NONHUMAN; POLYMERASE CHAIN REACTION; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; QUANTITATIVE ANALYSIS; RAT; SIGNAL TRANSDUCTION; WESTERN BLOTTING; ANIMAL; BRAIN TUMOR; ENZYMOLOGY; GENE EXPRESSION PROFILING; GENETICS; IMMUNOLOGY; METABOLISM; PATHOLOGY; WISTAR RAT;

ANIMALS; BRAIN NEOPLASMS; DOWN-REGULATION; GENE EXPRESSION PROFILING; GLIOBLASTOMA; HUMANS; I-KAPPA B KINASE; MACROPHAGES; MALE; MICROGLIA; RATS; RATS, WISTAR;

EID: 84946025187     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.5310     Document Type: Article

References (54)

1. Yang I, Han SJ, Kaur G, Crane C, Parsa AT. The role of microglia in central nervous system immunity and glioma immunology. J Clin Neurosci. 2010; 17:6-10.
2. Kmiecik J, Poli A, Brons NH, Waha A, Eide GE, Enger P, Zimmer J, Chekenya M. Elevated CD3+ and CD8+ tumorinfiltrating immune cells correlate with prolonged survival in glioblastoma patients despite integrated immunosuppressive mechanisms in the tumor microenvironment and at the systemic level. J Neuroimmunol. 2013; 264:71-83.
3. Glass R, Synowitz M. CNS macrophages and peripheral myeloid cells in brain tumours. Acta Neuropathol. 2014; 128:347-362.
4. da Fonseca AC, Badie B. Microglia and macrophages in malignant gliomas: recent discoveries and implications for promising therapies. Clin Dev Immunol. 2013; 2013:264124.
5. El Andaloussi A, Lesniak MS. An increase in CD4+CD25+FOXP3+ regulatory T cells in tumorinfiltrating lymphocytes of human glioblastoma multiforme. Neuro Oncol. 2006; 8:234-243.
6. Heimberger AB, Abou-Ghazal M, Reina-Ortiz C, Yang DS, Sun W, Qiao W, Hiraoka N, Fuller GN. Incidence and prognostic impact of FoxP3+ regulatory T cells in human gliomas. Clin Cancer Res. 2008; 14:5166-5172.
7. Waziri A. Glioblastoma-derived mechanisms of systemic immunosuppression. Neurosurg Clin N Am. 2010; 21:31-42.
8. Heimberger AB, Sampson JH. Immunotherapy coming of age: what will it take to make it standard of care for glioblastoma? Neuro Oncol. 2011; 13:3-13.
9. Klein R, Roggendorf W. Increased microglia proliferation separates pilocytic astrocytomas from diffuse astrocytomas: a double labeling study. Acta Neuropathol. 2001; 101:245-248.
10. Morimura T, Neuchrist C, Kitz K, Budka H, Scheiner O, Kraft D, Lassmann H. Monocyte subpopulations in human gliomas: expression of Fc and complement receptors and correlation with tumor proliferation. Acta Neuropathol. 1990; 80:287-294.
11. Rodrigues JC, Gonzalez GC, Zhang L, Ibrahim G, Kelly JJ, Gustafson MP, Lin Y, Dietz AB, Forsyth PA, Yong VW, Parney IF. Normal human monocytes exposed to glioma cells acquire myeloid-derived suppressor cell-like properties. Neuro Oncol. 2010; 12:351-365.
12. Komohara Y, Ohnishi K, Kuratsu J, Takeya M. Possible involvement of the M2 anti-inflammatory macrophage phenotype in growth of human gliomas. J Pathol. 2008; 216:15-24.
13. Parney IF, Waldron JS, Parsa AT. Flow cytometry and in vitro analysis of human glioma-associated macrophages. Laboratory investigation. J Neurosurg. 2009; 110:572-582.
14. Hussain SF, Yang D, Suki D, Grimm E, Heimberger AB. Innate immune functions of microglia isolated from human glioma patients. J Transl Med. 2006; 4:15.
15. Hussain SF, Yang D, Suki D, Aldape K, Grimm E, Heimberger AB. The role of human glioma-infiltrating microglia/macrophages in mediating antitumor immune responses. Neuro Oncol. 2006; 8:261-279.
16. Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest. 2012; 122:787-795.
17. Gordon S, Martinez FO. Alternative activation of macrophages: mechanism and functions. Immunity. 2010; 32:593-604.
18. Kong LY, Wu AS, Doucette T, Wei J, Priebe W, Fuller GN, Qiao W, Sawaya R, Rao G, Heimberger AB. Intratumoral mediated immunosuppression is prognostic in genetically engineered murine models of glioma and correlates to immunotherapeutic responses. Clin Cancer Res. 2010; 16:5722-5733.
19. Markovic DS, Glass R, Synowitz M, Rooijen N, Kettenmann H. Microglia stimulate the invasiveness of glioma cells by increasing the activity of metalloprotease-2. J Neuropathol Exp Neurol. 2005; 64:754-762.
20. Markovic DS, Vinnakota K, Chirasani S, Synowitz M, Raguet H, Stock K, Sliwa M, Lehmann S, Kälin R, van Rooijen N, Holmbeck K, Heppner FL, Kiwit J, Matyash V, Lehnardt S, Kaminska B, et al. Gliomas induce and exploit microglial MT1-MMP expression for tumor expansion. Proc Natl Acad Sci U S A. 2009; 106:12530-12535.
21. Sliwa M, Markovic D, Gabrusiewicz K, Synowitz M, Glass R, Zawadzka M, Wesolowska A, Kettenmann H, Kaminska B. The invasion promoting effect of microglia on glioblastoma cells is inhibited by cyclosporin A. Brain. 2007; 130:476-489.
22. Wesolowska A, Kwiatkowska A, Slomnicki L, Dembinski M, Master A, Sliwa M, Franciszkiewicz K, Chouaib S, Kaminska B. Microglia-derived TGF-beta as an important regulator of glioblastoma invasion-an inhibition of TGF-beta-dependent effects by shRNA against human TGF-beta type II receptor. Oncogene. 2008; 27:918-930.
23. Sielska M, Przanowski P, Wylot B, Gabrusiewicz K, Maleszewska M, Kijewska M, Zawadzka M, Kucharska J, Vinnakota K, Kettenmann H, Kotulska K, Grajkowska W, Kaminska B. Distinct roles of CSF family cytokines in macrophage infiltration and activation in glioma progression and injury response. J Pathol. 2013; 230:310-321.
24. Wei J, Gabrusiewicz K, Heimberger A. The controversial role of microglia in malignant gliomas. Clin Dev Immunol. 2013; 2013:285246.
25. Gabrusiewicz K, Ellert-Miklaszewska A, Lipko M, Sielska M, Frankowska M, Kaminska B. Characteristics of the alternative phenotype of microglia/macrophages and its modulation in experimental gliomas. PLoS One. 2011; 6:e23902.
26. Ellert-Miklaszewska A, Dabrowski M, Lipko M, Sliwa M, Maleszewska M, Kaminska B. Molecular definition of the pro-tumorigenic phenotype of glioma-activated microglia. Glia. 2013; 61:1178-1190.
27. van den Boom J, Wolter M, Kuick R, Misek DE, Youkilis AS, Wechsler DS, Sommer C, Reifenberger G, Hanash SM. Characterization of gene expression profiles associated with glioma progression using oligonucleotide-based microarray analysis and real-time reverse transcription-polymerase chain reaction. Am J Pathol. 2003; 163:1033-1043.
28. Phillips HS, Kharbanda S, Chen R, Forrest WF, Soriano RH, Wu TD, Misra A, Nigro JM, Colman H, Soroceanu L, Williams PM, Modrusan Z, Feuerstein BG, Aldape K. Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell. 2006; 9:157-173.
29. Reddy SP, Britto R, Vinnakota K, Aparna H, Sreepathi HK, Thota B, Kumari A, Shilpa BM, Vrinda M, Umesh S, Samuel C, Shetty M, Tandon A, Pandey P, Hegde S, Hegde AS, et al. Novel glioblastoma markers with diagnostic and prognostic value identified through transcriptome analysis. Clin Cancer Res. 2008; 14:2978-2987.
30. Gravendeel LA, Kouwenhoven MC, Gevaert O, de Rooi JJ, Stubbs AP, Duijm JE, Daemen A, Bleeker FE, Bralten LB, Kloosterhof NK, De Moor B, Eilers PH, van der Spek PJ, Kros JM, Sillevis Smitt PA, van den Bent MJ, et al. Intrinsic gene expression profiles of gliomas are a better predictor of survival than histology. Cancer Res. 2009; 69:9065-9072.
31. Vauléon E, Tony A, Hamlat A, Etcheverry A, Chiforeanu DC, Menei P, Mosser J, Quillien V, Aubry M. Immune genes are associated with human glioblastoma pathology and patient survival. BMC Med Genomics. 2012; 5:41.
32. Donson AM, Birks DK, Schittone SA, KleinschmidtDeMasters BK, Sun DY, Hemenway MF, Handler MH, Waziri AE, Wang M, Foreman NK. Increased immune gene expression and immune cell infiltration in highgrade astrocytoma distinguish long-term from short-term survivors. J Immunol. 2012; 189:1920-1927.
33. Mieczkowski J, Tyburczy ME, Dabrowski M, Pokarowski P. Probe set filtering increases correlation between Affymetrix GeneChip and qRT-PCR expression measurements. BMC Bioinformatics. 2010; 11:104.
34. Kanehisa M, Goto S, Furumichi M, Tanabe M, Hirakawa M. KEGG for representation and analysis of molecular networks involving diseases and drugs. Nucleic Acids Res. 2010; 38:D355-360.
35. Natoli G. NF-κB and chromatin: ten years on the path from basic mechanisms to candidate drugs. Immunol Rev. 2012; 246:183-192.
36. Häcker H, Karin M. Regulation and function of IKK and IKK-related kinases. Sci STKE 2006. 2006; 357:re13.
37. Huang H, Hara A, Homma T, Yonekawa Y, Ohgaki H. Altered expression of immune defense genes in pilocytic astrocytomas. J Neuropathol Exp Neurol. 2005; 64:891-901.
38. Prosniak M, Harshyne LA, Andrews DW, Kenyon LC, Bedelbaeva K, Apanasovich TV, Heber-Katz E, Curtis MT, Cotzia P, Hooper DC. Glioma grade is associated with the accumulation and activity of cells bearing M2 monocyte markers. Clin Cancer Res. 2013; 19:3776-3786.
39. Whitton PS. Inflammation as a causative factor in the aetiology of Parkinson's disease. Br J Pharmacol. 2007; 150:963-976.
40. Chen C, Xu T, Chen J, Zhou J, Yan Y, Lu Y, Wu S. Allergy and risk of glioma: a meta-analysis. Eur J Neurol. 2011; 18:387-395.
41. Engler JR, Robinson AE, Smirnov I, Hodgson JG, Berger MS, Gupta N, James CD, Molinaro A, Phillips JJ. Increased microglia/macrophage gene expression in a subset of adult and pediatric astrocytomas. PLoS One. 2012; 7:e43339.
42. Rao P, Hayden MS, Long M, Scott ML, West AP, Zhang D, Oeckinghaus A, Lynch C, Hoffmann A, Baltimore D, Ghosh S. IkappaBbeta acts to inhibit and activate gene expression during the inflammatory response. Nature. 2010; 466:1115-1119.
43. Fong CH, Bebien M, Didierlaurent A, Nebauer R, Hussell T, Broide D, Karin M, Lawrence T. An antiinflammatory role for IKKbeta through the inhibition of "classical" macrophage activation. J Exp Med. 2008; 205:1269-1276.
44. Cho IH, Hong J, Suh EC, Kim JH, Lee H, Lee JE, Lee S, Kim CH, Kim DW, Jo EK, Lee KE, Karin M, Lee SJ. Role of microglial IKKbeta in kainic acid-induced hippocampal neuronal cell death. Brain. 2008; 131:3019-3033.
45. Greten FR, Eckmann L, Greten TF, Park JM, Li ZW, Egan LJ, KagnoffMF, Karin M. IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell. 2004; 118:285-296.
46. Hagemann T, Biswas SK, Lawrence T, Sica A, Lewis CE. Regulation of macrophage function in tumors: the multifaceted role of NF-kappaB. Blood. 2009; 113:3139-3146.
47. Yang J, Hawkins O, Barham W, Gilchuk P, Boothby M, Ayers GD, Joyce S, Karin M, Yull F, Richmond A. Myeloid IKKβ Promotes Anti-tumor Immunity by Modulating CCL11 and the Innate Immune Response. Cancer Res. 2014;.
48. Gehrmann J, Banati RB, Kreutzberg GW. Microglia in the immune surveillance of the brain: human microglia constitutively express HLA-DR molecules. J Neuroimmunol. 1993; 48:189-198.
49. Sharma MK, Mansur DB, Reifenberger G, Perry A, Leonard JR, Aldape KD, Albin MG, Emnett RJ, Loeser S, Watson MA, Nagarajan R, Gutmann DH. Distinct genetic signatures among pilocytic astrocytomas relate to their brain region origin. Cancer Res. 2007; 67:890-900.
50. Turkheimer FE, Roncaroli F, Hennuy B, Herens C, Nguyen M, Martin D, Evrard A, Bours V, Boniver J, Deprez M. Chromosomal patterns of gene expression from microarray data: methodology, validation and clinical relevance in gliomas. BMC Bioinformatics. 2006; 7:526.
51. Liu T, Papagiannakopoulos T, Puskar K, Qi S, Santiago F, Clay W, Lao K, Lee Y, Nelson SF, Kornblum HI, Doyle F, Petzold L, Shraiman B, Kosik KS. Detection of a microRNA signal in an in vivo expression set of mRNAs. PLoS One. 2007; 2:e804.
52. Liang Y, Diehn M, Watson N, Bollen AW, Aldape KD, Nicholas MK, Lamborn KR, Berger MS, Botstein D, Brown PO, Israel MA. Gene expression profiling reveals molecularly and clinically distinct subtypes of glioblastoma multiforme. Proc Natl Acad Sci U S A. 2005; 102:5814-5819.
53. Ducray F, Idbaih A, de Reyniès A, Bièche I, Thillet J, Mokhtari K, Lair S, Marie Y, Paris S, Vidaud M, Hoang-Xuan K, Delattre O, Delattre JY, Sanson M. Anaplastic oligodendrogliomas with 1p19q codeletion have a proneural gene expression profile. Mol Cancer. 2008; 7:41.
54. Pera J, Zawadzka M, Kaminska B, Szczudlik A. Influence of chemical and ischemic preconditioning on cytokine expression after focal brain ischemia. J Neurosci Res. 2004; 78:132-40.