Schistosoma hematobium soluble egg antigens induce proliferation of urothelial and endothelial cells

Abstract

Bladder carcinoma accounts for 26% of reported human malignancies in Egypt, and has been strongly associated with urinary schistosomiasis. Nevertheless, the immediate role of schistosomal egg proteins in bladder carcinogenesis is unexplored. We investigated the effects of crude soluble egg antigens (SEA) of Schistosoma hematobium on urothelial cell proliferation. The proliferation of bovine endothelial Endo, human urothelial J82 and smooth muscle SMC cell lines was assessed by low-density growth assays. SEA induced proliferation of both J82 and Endo cells in a dose-dependent fashion, but not SMC. Preboiling or proteinase K treatment of SEA abolished its effect. In addition, SEA enhanced urothelial expression of B-cell translocation protein (BTG1) and human proliferating cell nuclear antigen (PCNA) mRNAs. Given the strong correlation between cell proliferation and carcinogenesis, the findings suggest that crude SEA may play some role in schistosomal bladder carcinogenesis.

Impact of density of schistosomal antigen expression in urinary bladder tissue on the stratification, cell type, and staging, and prognosis of carcinoma of the bladder in Egyptian patients

“…The impact of schistosomiasis on the urinary bladder had been considered to be a promoter for carcinoma [12,13] which was confirmed in our clinical study. The presence of strong intensity and high density in high stages of tumours denoted the schistosomal antigen tumour genesis in urothelial carcinoma associated with schistosomiasis [12].…”

Soluble egg antigen of Schistosoma Haematobiuminduces HCV replication in PBMC from patients with chronic HCV infection

“…In this regard both SEA and the commercial cellular mitogen PHA exerted similar magnitudes of DNA replication in the studied controls within 7 days of culture. Reports on other cell systems from our laboratory [ 14 ] and others [ 26 , 27 ] demonstrated that SEA associated cell proliferation involved up-regulation of cell cycle controlling genes such as peripheral cell nuclear antigen (PCNA) and B-cell translocation gene 1 (BTG1). Previous studies [ 28 ] reported that most soluble egg antigen fractions elicited in vitro granuloma reactions by PBMC of almost all Schitosoma haematobium infected patients and in vivo via endothelial cell proliferation [ 12 , 29 ] Conversely, separated soluble adult-worm antigens failed to stimulate PBMC of infected patients to form granulomas [ 28 ] suggesting that SEA contains unique factor (s) which are lacking in adult worm antigens.…”

“…The majority of these have focused on the role of growth factor rich soluble egg antigen (SEA), in contrary to adult worm soluble antigens, on angiogenic processes and granuloma formation mediated by peripheral blood mononuclear cell (PBMC) [ 11 ] and endothelial cell proliferation [ 12 ] through distinct intracellular signaling pathway[ 13 ]. Such mitogenic activity of SEA was shown to be cell specific, dose dependent and involves up regulation of cell cycle engine promoting genes [ 14 ].…”

Schistosoma mansoni soluble egg antigens enhance HCV replication in mammalian cells

“…The early detection of the virus genome in RNA extracted from infected cells in the presence of SEA may be interpreted in light of a previous report describing the proliferative effect of such antigens [38] that might give more space for enhancing viral replication.…”