Microglia/macrophages promote glioma progression.
Gliomas are highly aggressive and accompanied by numerous microglia/macrophages (MG/MP) in and about the tumor. Little is known about what MG/MP do in this setting, or whether modulating MG/MP activation might affect glioma progression. Here, we used a glioma-microglia in culture system to establish the effects the tumor and microglia have on each other. We assessed glioma progression in vivo after MG/MP ablation or in the setting of exaggerated MG/MP activation. We show that glioma cells activate microglia but inhibit their phagocytic activities. Local ablation of MG/MP in vivo decreased tumor size and improved survival curves. Conversely, pharmacological activation of MG/MP increased glioma size through stimulating tumor proliferation and inhibiting apoptosis. In agreement with recent reports, expression of the chemokine CCL21 is enhanced after MG/MP activation and correlates with tumor growth. Taken together, our findings demonstrate that inhibition of MG/MP activation may constitute a new and effective contribution towards suppressing glioma proliferation.
Molecular and Cellular Biology Program, Stony Brook University, Stony Brook, New York 11794-8651, USA.
Haiyan
H
Zhai
Frank L
FL
Heppner
Stella E
SE
Tsirka
D000818:Animals; D000831:Animals, Newborn; D001932:Brain Neoplasms / Q000209:etiology* / Q000473:pathology*; D002450:Cell Communication / Q000502:physiology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D018450:Disease Progression; D005260:Female; D005910:Glioma / Q000209:etiology* / Q000473:pathology*; D008264:Macrophages / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017628:Microglia / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000473:pathology*
J Immunol. 1997 Nov 1;159(9):4415-25
9379040
J Neurosci. 1993 Feb;13(2):455-66
7678855
Cancer Immunol Immunother. 2010 Apr;59(4):541-51
19798500
Acta Neuropathol. 2002 Apr;103(4):351-5
11904754
J Neurooncol. 2004 Nov;70(2):217-28
15674479
J Immunol. 1993 Aug 15;151(4):2150-8
8345199
Nat Cell Biol. 2001 Dec;3(12):1035-42
11781564
Infect Immun. 1994 Jun;62(6):2649-52
8188392
Glia. 2001 Apr 15;34(2):121-33
11307161
Brain Res. 1992 Jan 31;571(1):19-25
1377084
Science. 2010 May 7;328(5979):749-52
20339029
Mol Cell Biochem. 1987 Jun;75(2):169-74
3627109
BMC Immunol. 2007 Jul 16;8:10
17634104
J Neurosci. 2005 Aug 17;25(33):7548-57
16107642
J Gen Virol. 1986 Sep;67 ( Pt 9):2001-4
3746258
Proc Natl Acad Sci U S A. 2009 Jul 28;106(30):12530-5
19617536
J Natl Cancer Inst. 1985 May;74(5):1079-83
3858577
Neurosci Lett. 1995 Aug 25;196(3):153-6
7501271
Mol Chem Neuropathol. 1994 Feb-Apr;21(2-3):177-88
8086034
Glia. 2002 Nov;40(2):252-9
12379912
J Neuropathol Exp Neurol. 2005 Sep;64(9):754-62
16141784
Exp Neurol. 2000 Jan;161(1):85-95
10683275
Cancer Treat Rep. 1981 Jul-Aug;65(7-8):673-5
6894714
Trends Neurosci. 1996 Aug;19(8):312-8
8843599
J Neurosci. 2002 May 1;22(9):3352-8
11978811
N Engl J Med. 2001 Jan 11;344(2):114-23
11150363
Stroke. 2005 Mar;36(3):613-8
15692122
J Neurooncol. 1998 Aug;39(1):1-18
9760066
J Mol Neurosci. 1999 Aug-Oct;13(1-2):177-85
10691304
Nat Med. 2005 Feb;11(2):146-52
15665833
J Neurochem. 1998 Nov;71(5):1837-45
9798907
J Neurosurg. 1995 May;82(5):864-73
7714613
Cancer Res. 2005 Apr 1;65(7):2964-71
15805300
Acta Neuropathol. 1996 Sep;92(3):288-93
8870831
Prog Neurobiol. 1999 Apr;57(6):563-81
10221782
Mol Cancer Ther. 2008 Apr;7(4):788-99
18375821
J Leukoc Biol. 2009 Nov;86(5):1065-73
19741157
Acta Neuropathol. 2001 Mar;101(3):245-8
11307624
Int J Cancer. 2010 Sep 1;127(5):1131-40
20027632
Biochim Biophys Acta. 1973 May 17;310(1):230-7
4710594
Immunol Rev. 2008 Apr;222:155-61
18364000
J Immunol. 1992 Mar 1;148(5):1404-10
1538124
Int J Cancer. 1999 Jul 2;82(1):12-6
10360813
Peptides. 1999;20(5):645-74
10465518
J Neuroimmunol. 2002 Dec;133(1-2):39-45
12446006
Curr Biol. 1998 Jan 1;8(1):19-25
9427623
Cancer Cell. 2007 Jun;11(6):526-38
17560334
J Natl Cancer Inst. 1999 Aug 18;91(16):1382-90
10451443
J Biol Chem. 1987 May 25;262(15):7053-7
3034878
Oncogene. 2008 Feb 7;27(7):918-30
17684491
Acta Neuropathol. 2002 Feb;103(2):171-8
11810184
J Transl Med. 2006 Mar 30;4:15
16573834
Mol Cancer Ther. 2007 Apr;6(4):1212-22
17406030
Neurobiol Dis. 2010 Jul;39(1):85-97
20382223
J Neurol Sci. 1991 Jan;101(1):47-58
2027027
J Immunol. 2002 Apr 1;168(7):3221-6
11907075
Brain Res Mol Brain Res. 1998 Jun 1;57(1):1-9
9630473
Int J Dev Neurosci. 1999 Aug-Oct;17(5-6):547-56
10571416
Cancer Res. 2010 Feb 15;70(4):1534-43
20145121
Neuropathol Appl Neurobiol. 1994 Apr;20(2):206-8
8072666
Glia. 2006 Nov 1;54(6):526-35
16906541
J Clin Oncol. 2005 Mar 20;23(9):1867-74
15774779
Acta Neuropathol. 1997 May;93(5):518-27
9144591
J Immunol. 2009 Jun 1;182(11):6771-8
19454672
Nat Rev Cancer. 2004 Jan;4(1):71-8
14708027
Anticancer Res. 1997 Sep-Oct;17(5A):3217-24
9413151
Neurosurgery. 1999 May;44(5):1077-82; discussion 1082-3
10232541
J Neurooncol. 2002 Jan;56(1):1-12
11949821
Acta Neuropathol. 1990;80(3):287-94
2399810
Cancer Res. 2007 Sep 15;67(18):8874-81
17875729
J Neurooncol. 2001 Jun;53(2):177-85
11716069