Secretion of functionally active complement factor H related protein 5 (FHR5) by primary tumour cells derived from Glioblastoma Multiforme patients

Immunobiology. 2019 Sep;224(5):625-631. doi: 10.1016/j.imbio.2019.07.006. Epub 2019 Aug 5.

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.

Keywords: FH; FHR5; Glioblastoma and complement.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Complement Activation
  • Complement C3-C5 Convertases / metabolism
  • Complement C3b / immunology
  • Complement System Proteins / biosynthesis*
  • Complement System Proteins / immunology
  • Complement System Proteins / metabolism
  • Glioblastoma / immunology
  • Glioblastoma / metabolism*
  • Hemolysis / immunology
  • Humans
  • Proteolysis

Substances

  • Biomarkers
  • CFHR5 protein, human
  • Complement C3b
  • Complement System Proteins
  • Complement C3-C5 Convertases