PD53-03: Schistosoma haematobium may promote bladder carcinogenesis through DNA binding of its homolog of the Interleukin-4-inducing principle from Schistosoma mansoni eggs

Derick Osakunor*, Washington, DC, Trevor Siggers, Boston, MA, Olivia Lamanna, Kenji Ishida, Washington , DC, Heather Hook, Boston, MA, Michael Hsieh, Washington, DC

Introduction: Urogenital schistosomiasis, caused by Schistosoma haematobium, is the most common form of schistosomiasis worldwide and is well-known for its association with bladder cancer. However, the underlying mechanisms for the causal link between S. haematobium and bladder cancer, are poorly understood. Interleukin-4-inducing principle from Schistosoma mansoni eggs (IPSE) is the most abundant secreted protein from eggs of all schistosome species and plays a major role in modulating host pathology. We have previously demonstrated that H-IPSE, the S. haematobium homolog of IPSE, is internalized by both endothelial and urothelial cells, drives endothelial and urothelial proliferation, and may thus be involved in S. haematobium-related carcinogenesis.

Methods: Here, we used protein binding microarray (PBM) technology and bioinformatics approaches to determine the specific DNA binding motifs of H-IPSE, and the downstream transcriptional events that result from DNA binding.

Results: Our results showed that DNA binding of H-IPSE is highly specific, and a DNA-binding motif of GGGTGGG was determined. The GGGTGGG sequence is recognized by the transcription factors PuF and Sall2, which are involved in tumor suppression by binding to the promoter of c-myc. Concurrent experiments with M-IPSE (the S. mansoni homolog) showed that M-IPSE has the DNA binding motif resembling GGGGGAAAA and is different from H-IPSE, although similar in their affinity for G-rich sequences.

Conclusions: Together, our results enabled us to identify novel molecular targets of H-IPSE that may explain its role in carcinogenesis. The differences in DNA binding motifs for H-IPSE and M-IPSE may likely explain why S. haematobium, but not S. mansoni, is carcinogenic.

Source of Funding: NIH R01DK113504