TY - JOUR
T1 - Differential responses of epithelial cells from urinary and biliary tract to eggs of Schistosoma haematobium and S. mansoni
AU - Nacif-Pimenta, Rafael
AU - da Silva Orfanó, Alessandra
AU - Mosley, Ilana A.
AU - Karinshak, Shannon E.
AU - Ishida, Kenji
AU - Mann, Victoria H.
AU - Coelho, Paulo Marcos Zech
AU - da Costa, José M.Correia
AU - Hsieh, Michael H.
AU - Brindley, Paul J.
AU - Rinaldi, Gabriel
N1 - Funding Information:
Rafael Nacif-Pimenta was supported by PhD fellowships from Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior (CAPES) and the Fundação de Amparo a Pesquisas de Minas Gerais (FAPEMIG). We thank Dra. Mónica C. Botelho, Department of Infectious Diseases, R&D Unit, INSA-National Health Institute Dr. Ricardo Jorge, Porto, Portugal & IPATIMUP, Institute of Pathology and Molecular Immunology of the University of Porto, Portugal for the HCV29 cell line and informative discussion, and Christian Owusu from the Wellcome Sanger Institute for expert technical assistance. Hamsters and mice infected with Schistosoma haematobium and S. mansoni, respectively, were provided by the NIAID Schistosomiasis Resource Center for distribution through BEI Resources, NIH-NIAID Contract HHSN272201000005I. We acknowledge support from the GW SPARC program (IAM) and award R01CA164719 from the National Cancer Institute (NCI), NIH. The content is solely the responsibility of the authors and does not necessarily represent the official views of CAPES, FAPEMIG, NCI or the NIH.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/7/24
Y1 - 2019/7/24
N2 - Chronic urogenital schistosomiasis can lead to squamous cell carcinoma of the bladder. The International Agency for Research on Cancer classifies the infection with S. haematobium as a group 1 carcinogen, a definitive cause of cancer. By contrast, hepatointestinal schistosomiasis due to the chronic infection with S. mansoni or S. japonicum associated with liver periportal fibrosis, does not apparently lead to malignancy. The effects of culturing human epithelial cells, HCV29, established from normal urothelium, and H69, established from cholangiocytes, in the presence of S. haematobium or S. mansoni eggs were investigated. Cell growth of cells co-cultured with schistosome eggs was monitored in real time, and gene expression analysis of oncogenesis, epithelial to mesenchymal transition and apoptosis pathways was undertaken. Schistosome eggs promoted proliferation of the urothelial cells but inhibited growth of cholangiocytes. In addition, the tumor suppressor P53 pathway was significantly downregulated when exposed to schistosome eggs, and downregulation of estrogen receptor was predicted in urothelial cells exposed only to S. haematobium eggs. Overall, cell proliferative responses were influenced by both the tissue origin of the epithelial cells and the schistosome species.
AB - Chronic urogenital schistosomiasis can lead to squamous cell carcinoma of the bladder. The International Agency for Research on Cancer classifies the infection with S. haematobium as a group 1 carcinogen, a definitive cause of cancer. By contrast, hepatointestinal schistosomiasis due to the chronic infection with S. mansoni or S. japonicum associated with liver periportal fibrosis, does not apparently lead to malignancy. The effects of culturing human epithelial cells, HCV29, established from normal urothelium, and H69, established from cholangiocytes, in the presence of S. haematobium or S. mansoni eggs were investigated. Cell growth of cells co-cultured with schistosome eggs was monitored in real time, and gene expression analysis of oncogenesis, epithelial to mesenchymal transition and apoptosis pathways was undertaken. Schistosome eggs promoted proliferation of the urothelial cells but inhibited growth of cholangiocytes. In addition, the tumor suppressor P53 pathway was significantly downregulated when exposed to schistosome eggs, and downregulation of estrogen receptor was predicted in urothelial cells exposed only to S. haematobium eggs. Overall, cell proliferative responses were influenced by both the tissue origin of the epithelial cells and the schistosome species.
KW - Animals
KW - Biliary Tract/metabolism
KW - Cell Line
KW - Coculture Techniques
KW - Colorectal Neoplasms/metabolism
KW - Epithelium/metabolism
KW - Estradiol/metabolism
KW - Humans
KW - Ovum
KW - Receptors, Estrogen/metabolism
KW - Schistosoma haematobium
KW - Schistosoma mansoni
KW - Schistosomiasis haematobia/pathology
KW - Schistosomiasis mansoni/pathology
KW - Signal Transduction
KW - Transcriptome
KW - Tumor Suppressor Protein p53/metabolism
KW - Urothelium/metabolism
UR - http://www.scopus.com/inward/record.url?scp=85069646310&partnerID=8YFLogxK
U2 - 10.1038/s41598-019-46917-y
DO - 10.1038/s41598-019-46917-y
M3 - Article
C2 - 31341177
AN - SCOPUS:85069646310
SN - 2045-2322
VL - 9
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 10731
ER -
