TY - JOUR
T1 - Secretion of functionally active complement factor H related protein 5 (FHR5) by primary tumour cells derived from Glioblastoma Multiforme patients
AU - DeCordova, Syreeta
AU - Abdelgany, Amr
AU - Murugaiah, Valarmathy
AU - Pathan, Ansar A.
AU - Nayak, Annapurna
AU - Walker, Tom
AU - Shastri, Abhishek
AU - Alrokayan, Salman H.
AU - Khan, Haseeb A.
AU - Singh, Shiv K.
AU - De Pennington, Nick
AU - Sim, Robert B.
AU - Kishore, Uday
N1 - Publisher Copyright:
© 2019 The Authors
PY - 2019/9
Y1 - 2019/9
N2 - The complement system is an important humoral immune surveillance mechanism against tumours. However, many malignant tumours are resistant to complement mediated lysis. Here, we report secretion of complement factor H related protein 5 (FHR5) by primary tumour cells derived from Glioblastoma multiforme (GBM) patients. We investigated whether the secreted FHR5 exhibited functional activity similar to factor H, including inhibition of complement mediated lysis, acting as a co-factor for factor I mediated cleavage of C3b, and decay acceleration of C3 convertase. Immunoblotting analysis of primary GBM cells (B30, B31 and B33) supernatant showed the active secretion of FHR5, but not of Factor H. ELISA revealed that the secretion of soluble GBM-FHR5 by cultured GBM cells increased in a time-dependent manner. Primary GBM-FHR5 inhibited complement mediated lysis, possessed co-factor activity for factor I mediated cleavage and displayed decay acceleration of C3 convertase. In summary, we detected the secretion of FHR5 by primary GBM cells B30, B31 and B33. The results demonstrated that GBM-FHR5 shares biological function with FH as a mechanism primary GBM cells potentially use to resist complement mediated lysis.
AB - The complement system is an important humoral immune surveillance mechanism against tumours. However, many malignant tumours are resistant to complement mediated lysis. Here, we report secretion of complement factor H related protein 5 (FHR5) by primary tumour cells derived from Glioblastoma multiforme (GBM) patients. We investigated whether the secreted FHR5 exhibited functional activity similar to factor H, including inhibition of complement mediated lysis, acting as a co-factor for factor I mediated cleavage of C3b, and decay acceleration of C3 convertase. Immunoblotting analysis of primary GBM cells (B30, B31 and B33) supernatant showed the active secretion of FHR5, but not of Factor H. ELISA revealed that the secretion of soluble GBM-FHR5 by cultured GBM cells increased in a time-dependent manner. Primary GBM-FHR5 inhibited complement mediated lysis, possessed co-factor activity for factor I mediated cleavage and displayed decay acceleration of C3 convertase. In summary, we detected the secretion of FHR5 by primary GBM cells B30, B31 and B33. The results demonstrated that GBM-FHR5 shares biological function with FH as a mechanism primary GBM cells potentially use to resist complement mediated lysis.
KW - FH
KW - FHR5
KW - Glioblastoma and complement
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U2 - 10.1016/j.imbio.2019.07.006
DO - 10.1016/j.imbio.2019.07.006
M3 - Article
C2 - 31519376
AN - SCOPUS:85071993453
SN - 0171-2985
VL - 224
SP - 625
EP - 631
JO - Immunobiology
JF - Immunobiology
IS - 5
ER -