TY - JOUR

T1 - A tumorigenic cell line derived from a hamster cholangiocarcinoma associated with Opisthorchis felineus liver fluke infection

AU - Mordvinov, Viatcheslav A.

AU - Minkova, Galina A.

AU - Kovner, Anna V.

AU - Ponomarev, Dmitriy V.

AU - Lvova, Maria N.

AU - Zaparina, Oxana

AU - Romanenko, Svetlana A.

AU - Shilov, Alexander G.

AU - Pakharukova, Maria Y.

N1 - Publisher Copyright: © 2021 Elsevier Inc. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/7/15

Y1 - 2021/7/15

N2 - Aims: The food-born trematode Opisthorchis felineus colonizes bile ducts of the liver of fish-eating mammals including humans. There is growing evidence that this liver fluke is a risk factor for cholangiocarcinoma (CCA). Cancer cell lines are necessary for drug screening and for identifying protein markers of CCA. The aim was to establish a cell line derived from cholangiocarcinoma associated with opisthorchiasis felinea. Main methods: Allotransplantation, immunohistochemistry, karyotype analysis, cell culture techniques, immunocytochemistry and real-time PCR. Key findings: Here we repot the establishment of first CCA cell line, CCA-OF, from a primary tumor of an experimental CCA in Syrian hamsters treated with low doses of dimethyl nitrosamine and associated with O. felineus infection. The cell line was found to be allotransplantable. Expression of epithelial and mesenchymal markers (cytokeratin 7, glycosyltransferase exostosin 1, Ca2+-dependent phospholipid-binding protein annexin A1 and vimentin) was demonstrated by immunostaining of the primary tumors, CCA-OF cells, and allotransplants. CCA-OF cells were found to express presumed CCA biomarkers previously detected in both human and experimental tumors associated with the liver fluke infection. The cells were diploid-like (2n = 42–46) with complex chromosomal rearrangements and have morphological features of epithelial-like cells. The usefulness of the CCA-OF cell model for antitumor activity testing was demonstrated by an analysis of effects of resveratrol treatment. It was shown that resveratrol treatment inhibited the proliferation and the migration ability of CCA-OF cells. Significance: Thus, the allotransplantable CCA-OF cell line can be used in studies on helminth-associated cholangiocarcinogenesis and for the testing of antitumor drugs.

AB - Aims: The food-born trematode Opisthorchis felineus colonizes bile ducts of the liver of fish-eating mammals including humans. There is growing evidence that this liver fluke is a risk factor for cholangiocarcinoma (CCA). Cancer cell lines are necessary for drug screening and for identifying protein markers of CCA. The aim was to establish a cell line derived from cholangiocarcinoma associated with opisthorchiasis felinea. Main methods: Allotransplantation, immunohistochemistry, karyotype analysis, cell culture techniques, immunocytochemistry and real-time PCR. Key findings: Here we repot the establishment of first CCA cell line, CCA-OF, from a primary tumor of an experimental CCA in Syrian hamsters treated with low doses of dimethyl nitrosamine and associated with O. felineus infection. The cell line was found to be allotransplantable. Expression of epithelial and mesenchymal markers (cytokeratin 7, glycosyltransferase exostosin 1, Ca2+-dependent phospholipid-binding protein annexin A1 and vimentin) was demonstrated by immunostaining of the primary tumors, CCA-OF cells, and allotransplants. CCA-OF cells were found to express presumed CCA biomarkers previously detected in both human and experimental tumors associated with the liver fluke infection. The cells were diploid-like (2n = 42–46) with complex chromosomal rearrangements and have morphological features of epithelial-like cells. The usefulness of the CCA-OF cell model for antitumor activity testing was demonstrated by an analysis of effects of resveratrol treatment. It was shown that resveratrol treatment inhibited the proliferation and the migration ability of CCA-OF cells. Significance: Thus, the allotransplantable CCA-OF cell line can be used in studies on helminth-associated cholangiocarcinogenesis and for the testing of antitumor drugs.

KW - Cell line

KW - Cholangiocarcinoma

KW - Experimental model

KW - Hamster

KW - Opisthorchis felineus

KW - Cell Line

KW - Epithelial Cells/metabolism

KW - Carcinogenesis/pathology

KW - Cricetinae/metabolism

KW - Animals

KW - Liver/metabolism

KW - Bile Ducts, Intrahepatic/metabolism

KW - Cholangiocarcinoma/metabolism

KW - Bile Duct Neoplasms/pathology

KW - Opisthorchiasis/complications

UR - http://www.scopus.com/inward/record.url?scp=85105830799&partnerID=8YFLogxK

U2 - 10.1016/j.lfs.2021.119494

DO - 10.1016/j.lfs.2021.119494

M3 - Article

C2 - 33862109

AN - SCOPUS:85105830799

VL - 277

SP - 119494

JO - Life Sciences

JF - Life Sciences

SN - 0024-3205

M1 - 119494

ER -