Research output: Contribution to journal › Article › peer-review
The EGFR Signaling Pathway Is Involved in the Biliary Intraepithelial Neoplasia Associated with Liver Fluke Infection. / Ponomarev, Dmitry V.; Zaparina, Oxana; Kovner, Anna et al.
In: Pathogens, Vol. 14, No. 7, 2025, p. 620.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - The EGFR Signaling Pathway Is Involved in the Biliary Intraepithelial Neoplasia Associated with Liver Fluke Infection
AU - Ponomarev, Dmitry V.
AU - Zaparina, Oxana
AU - Kovner, Anna
AU - Hadieva, Elena
AU - Persidskij, Mikhail
AU - Pakharukova, Maria
N1 - The research was funded by the Russian Science Foundation (Project No. 24-25-00080) (O.Z.).
PY - 2025
Y1 - 2025
N2 - Foodborne trematode infections are recognized as a significant risk factor for cholangiocarcinoma (CCA) in endemic regions. Infection with the liver fluke Opisthorchis felineus induces precursor lesions of CCA, including the biliary intraepithelial neoplasia. The mechanisms underlying liver-fluke-associated neoplasia remain poorly understood. This study aims to identify the role of EGFR and Toll-like receptor 4-associated signaling pathways in bile duct epithelial neoplasia linked to liver fluke infection in patients, animal models, and cell models. Elevated levels of EGFR and phosphorylated EGFR were observed in the bile duct epithelium of patients with cholangiocarcinoma, as well as in the bile duct epithelium of laboratory hamsters. The EGFR content correlated with the degree of bile duct epithelial neoplasia. Additionally, a significant increase in the cell proliferation and migration rates of human H69 cholangiocytes was found, whereas those of HepG2 hepatoma cells remained unaffected following the helminth excretory–secretory product (ESP) treatment. An EGFR inhibitor eliminated the enhanced cell proliferation (p = 0.005) and migration (p = 0.001) rates. Similar outcomes were achieved using Marimastat, an inhibitor of TLR-4-associated metalloproteinases. Thus, our study unveils novel avenues for exploring the mechanisms of helminth-associated carcinogenesis and for identifying key components of ESPs that mediate their mitogenic effects.
AB - Foodborne trematode infections are recognized as a significant risk factor for cholangiocarcinoma (CCA) in endemic regions. Infection with the liver fluke Opisthorchis felineus induces precursor lesions of CCA, including the biliary intraepithelial neoplasia. The mechanisms underlying liver-fluke-associated neoplasia remain poorly understood. This study aims to identify the role of EGFR and Toll-like receptor 4-associated signaling pathways in bile duct epithelial neoplasia linked to liver fluke infection in patients, animal models, and cell models. Elevated levels of EGFR and phosphorylated EGFR were observed in the bile duct epithelium of patients with cholangiocarcinoma, as well as in the bile duct epithelium of laboratory hamsters. The EGFR content correlated with the degree of bile duct epithelial neoplasia. Additionally, a significant increase in the cell proliferation and migration rates of human H69 cholangiocytes was found, whereas those of HepG2 hepatoma cells remained unaffected following the helminth excretory–secretory product (ESP) treatment. An EGFR inhibitor eliminated the enhanced cell proliferation (p = 0.005) and migration (p = 0.001) rates. Similar outcomes were achieved using Marimastat, an inhibitor of TLR-4-associated metalloproteinases. Thus, our study unveils novel avenues for exploring the mechanisms of helminth-associated carcinogenesis and for identifying key components of ESPs that mediate their mitogenic effects.
UR - https://www.mendeley.com/catalogue/738c4855-bc56-32dc-a5cc-9872c6cf605a/
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=105011499506&origin=inward
U2 - 10.3390/pathogens14070620
DO - 10.3390/pathogens14070620
M3 - Article
C2 - 40732668
VL - 14
SP - 620
JO - Pathogens
JF - Pathogens
SN - 2076-0817
IS - 7
ER -
ID: 68614525