Tumour-like phenotypes in urothelial cells after exposure to antigens from eggs of Schistosoma haematobium: An oestrogen–DNA adducts mediated pathway?

Abstract

a b s t r a c tChronic infection with the blood fluke, Schistosoma haematobium, is associated with squamous cell carcinoma of the bladder. Previously, it has been shown that soluble extracts of mixed sex adult S. haematobium worms (SWAP) are tumourigenic, both in vitro and in vivo. In addition, oestrogen-related molecules in SWAP of S. haematobium down-regulate oestrogen receptors (ERs) alpha and beta in oestrogen responsive cells. Moreover, schistosome oestrogens occur in sera of persons with schistosomiasis haematobia and repress transcription of ERs in urothelial cells. Given that eggs of S. haematobium are the developmental stage directly responsible for urogenital disease during schistosomiasis haematobia, we suspected that soluble antigens from S. haematobium eggs exhibit similar or more potent tumorigenic capacity. Here we investigated the tumorigenic potential of soluble egg antigens (Sh-SEA) of S. haematobium and the endocrine system in favouring parasitism by schistosomes. The findings confirmed that 6.25 lg/ml of Sh-SEA was enough to stimulate cell proliferation, reduce apoptosis and increase oxidative stress of Sh-SEA-exposed urothelial cells. In addition, genotoxic effects of Sh-SEA on these cells were determined by using alkaline single-cell gel electrophoresis (Comet). Furthermore, Liquid Chromatography Diode Array Detection Electron Spray Ionisation Mass Spectrometry indicated the presence of catechol-oestrogens in S. haematobium SEA. A prospective oestrogen-DNA adduct mediated pathway in S. haematobium egg induced bladder cancer is also discussed. Ó

The role of estrogens and estrogen receptor signaling pathways in cancer and infertility: the case of schistosomes

“…Recently, estrogen-like metabolites were detected by LC-MS in urine of S. haematobium-infected women. These metabolites are similar to those identified previously in the adult worm and egg stages of S. haematobium [1]. The presence of estrogen-like metabolites during FGS was statistically associated with self-reported infertility [11].…”

“…Metabolism of estrogens and the production of depurinating estrogen-DNA adducts can be implicated in a pathway underlying S. haematobium-promoted host cell DNA damage, leading eventually to cell transformation. The carcinogenic effect of this estrogen-DNA adductmediated pathway could explain the link between chronic schistosomiasis haematobia and SCC of the bladder [1]. We anticipate that these findings will contribute to understanding how schistosomiasis haematobia leads to SCC of the bladder.…”

“…The majority of these compounds are catechol estrogens [1]. Catechol estrogens are formed by hydroxylation on the steroid aromatic ring A. Hydroxylation of both C-2 and C-3 on a steroid ring was apparent and suffered further oxidation into an estradiol-2,3-quinone.…”

“…Given the context of the unarguable link between S. haematobium infection and bladder cancer, the presence of putative carcinogenic molecules in S. haematobium eggs hopefully may have practical consequences for new approaches to disease control [1,35]. Metabolism of estrogens and the production of depurinating estrogen-DNA adducts can be implicated in a pathway underlying S. haematobium-promoted host cell DNA damage, leading eventually to cell transformation.…”

“…From these, 20 million have severe disease and 120 million are considered symptomatic. Risk of infection affects 600 million others including travelers from developed countries [1].…”