Schistosoma mansoni eggs induce Wnt/\u03b2-catenin signaling and activate the protooncogene c-Jun in human and hamster colon

Jakob Weglage,Kernt Köhler,Jörn Pons-Kühnemann,Christoph G Grevelding,Peter J Wild ,Celina Wulz,Thomas Quack,Margarete Odenthal,F Wolters ,Heike Mueller,Uta Drebber,L Hehr ,A Baier ,Felix Hempel,A Tschuschner ,Maha El Arousy,Katrin Bankov,Karuna Irungbam,Leandra Náira Zambelli Ramalho ,Gabriele Schramm,Jonas Tschammer,Jakob Lichtenberger,Verena Von Buelow,Elke Roeb,Thomas Longerich,M Roderfeld

doi:10.1038/s41598-020-79450-4

Abstract

Schistosomiasis (bilharzia) is a neglected tropical disease caused by parasitic flatworms of the genus Schistosoma, with considerable morbidity in parts of the Middle East, South America, Southeast Asia, in sub-Saharan Africa, and particularly also in Europe. The WHO describes an increasing global health burden with more than 290 million people threatened by the disease and a potential to spread into regions with temperate climates like Corsica, France. The aim of our study was to investigate the influence of S. mansoni infection on colorectal carcinogenic signaling pathways in vivo and in vitro. S. mansoni infection, soluble egg antigens (SEA) and the Interleukin-4-inducing principle from S. mansoni eggs induce Wnt/β-catenin signaling and the protooncogene c-Jun as well as downstream factor Cyclin D1 and markers for DNA-damage, such as Parp1 and γH2a.x in enterocytes. The presence of these characteristic hallmarks of colorectal carcinogenesis was confirmed in colon biopsies from S. mansoni-infected patients demonstrating the clinical relevance of our findings. For the first time it was shown that S. mansoni SEA may be involved in the induction of colorectal carcinoma-associated signaling pathways.

Highlights

Schistosomiasis is a neglected tropical disease caused by parasitic flatworms of the genus Schistosoma, with considerable morbidity in parts of the Middle East, South America, Southeast Asia, in sub-Saharan Africa, and in Europe
It has been suggested that the persistent establishment of the tropical disease in Europe relies on the preadaptation of schistosomes and the adaptation of secondary hosts to overwinter in countries like France, Italy, Portugal, Spain, and Greece[6]
The Human Phospho-Kinase Array is a rapid and sensitive tool to simultaneously detect the relative levels of phosphorylation of kinases and two related total proteins, which is essential for understanding how cells recognize and respond to changes in their environment. cAMP-response element binding protein (CREB S133), AMP-dependent Kinase (AMPKa1 T183), Heat shock protein 27 (Hsp[27] S78/S82), Epidermal Growth Factor Receptor (EGFR Y1086), Gsk3β S21/S9, β-catenin, and other factors were induced by stimulation of the human epithelial cell line SW620 with soluble egg antigens (SEA) (Fig. 1a,b)

Summary

Introduction

Schistosomiasis (bilharzia) is a neglected tropical disease caused by parasitic flatworms of the genus Schistosoma, with considerable morbidity in parts of the Middle East, South America, Southeast Asia, in sub-Saharan Africa, and in Europe. S. mansoni infection, soluble egg antigens (SEA) and the Interleukin-4-inducing principle from S. mansoni eggs induce Wnt/β-catenin signaling and the protooncogene c-Jun as well as downstream factor Cyclin D1 and markers for DNA-damage, such as Parp[1] and γH2a.x in enterocytes. The presence of these characteristic hallmarks of colorectal carcinogenesis was confirmed in colon biopsies from S. mansoniinfected patients demonstrating the clinical relevance of our findings. Schistosomiasis is diagnosed by the detection of parasite eggs in stool (S. mansoni, S. japonicum) or urine (S. haematobium) samples or, if accessible, by serological and immunological tests[1]

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