Abstract
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.
Highlights
Glioblastoma multiforme (GBM) is the most lethal brain tumour in adults with a median survival of less than 15 months (Ohgaki et al, 2004)
There are studies which show that factor H related protein 5 (FHR5) has a complement “activating” role (Goicoechea de Jorge et al, 2013) whereas it is reported that FHR5 can inhibit complement (McRae et al, 2005)
We investigated whether primary GBM cells would express the same factor H family proteins and if the endogenous product would inhibit or activate complement
Summary
Glioblastoma multiforme (GBM) is the most lethal brain tumour in adults with a median survival of less than 15 months (Ohgaki et al, 2004). One of the biggest clinical challenges in the treatment of GBM is the highly aggressive behaviour of cells that prevent complete surgical resection and enhance resistance to conventional radio- and chemotherapy (Ohgaki et al, 2004; Furnari et al, 2007). Even with complete surgical resection, the long-term survival of GBM patients remains very poor due to a high recurrence rate (Ohgaki et al, 2004). GBM is most often de novo (primary GBM), which develops quickly within a three-month
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