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Review
. 2018 Sep 12;6(1):91.
doi: 10.1186/s40478-018-0591-4.

The complement system in glioblastoma multiforme

T A M Bouwens van der Vlis  1   2   3 , J M Kros  4 , D A M Mustafa  3 , R T A van Wijck  5 , L Ackermans  2 , P M van Hagen  5   6 , P J van der Spek  1   3
Affiliations
Review

The complement system in glioblastoma multiforme

T A M Bouwens van der Vlis et al. Acta Neuropathol Commun. .

Abstract

The human complement system is represents the main effector arm of innate immunity and its ambivalent function in cancer has been subject of ongoing dispute. Glioma stem-like cells (GSC) residing in specific niches within glioblastomas (GBM) are capable of self-renewal and tumor proliferation. Recent data are indicative of the influence of the complement system on the maintenance of these cells. It appears that the role of the complement system in glial tumorigenesis, particularly its influence on GSC niches and GSC maintenance, is significant and warrants further exploration for therapeutic interventions.

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Competing interest

The authors whose names are listed above certify that they have no affiliations with or involvement in any organization or entity with any fi nancial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

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Figures

Fig. 1
Fig. 1
Schematic and simplified representation of the complement system. Complement regulatory proteins, both fluid-phase and membrane- bound are coloured light grey. C1INH: C1-inhibitor; CD46: Membrane Cofactor Protein; CD55: Complement decay-accelerating factor; FI: Complement factor I; CR1: Complement receptor type 1; FH: Complement factor H; C4BP: C4bbinding protein
Fig. 2
Fig. 2
Proposed interaction of complement C3a and C5a with GSC regulatory mechanisms. C5a-C5aR interaction activates PI3K/Akt/mTOR signaling and PKCζ but suppresses p21 with subsequent OCT-4 activation. Intracellular activation of C3a by cathepsin-L may occur, thereby sustaining basal mTOR activation. Either intracellular or extracellular derived C3a phosphorylates STAT-3 and causes an increase of SOX-2 expression
Fig. 3
Fig. 3
Graphical summary of the potential actions of the complement system in the glial tumor microenvironment
See this image and copyright information in PMC

References

    1. Afshar-Kharghan V. The role of the complement system in cancer. J Clin Invest. 2017;127:780–789. doi: 10.1172/JCI90962. - DOI - PMC - PubMed
    1. Ajona D, Ortiz-Espinosa S, Moreno H, Lozano T, Pajares MJ, Agorreta J, Bertolo C, Lasarte JJ, Vicent S, Hoehlig K, et al. A combined PD-1/C5a blockade synergistically protects against lung Cancer growth and metastasis. Cancer discovery. 2017;7:694–703. doi: 10.1158/2159-8290.CD-16-1184. - DOI - PubMed
    1. Bao S, Wu Q, Sathornsumetee S, Hao Y, Li Z, Hjelmeland AB, Shi Q, McLendon RE, Bigner DD, Rich JN. Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor. Cancer Res. 2006;66:7843–7848. doi: 10.1158/0008-5472.CAN-06-1010. - DOI - PubMed
    1. Benzaquen LR, Nicholson-Weller A, Halperin JA. Terminal complement proteins C5b-9 release basic fibroblast growth factor and platelet-derived growth factor from endothelial cells. J Exp Med. 1994;179:985–992. doi: 10.1084/jem.179.3.985. - DOI - PMC - PubMed
    1. Bohlson SS, O'Conner SD, Hulsebus HJ, Ho MM, Fraser DA. Complement, c1q, and c1q-related molecules regulate macrophage polarization. Front Immunol. 2014;5:402. doi: 10.3389/fimmu.2014.00402. - DOI - PMC - PubMed

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