Suppression of trophoblast cell surface antigen 2 enhances proliferation and migration in liver fluke-associated cholangiocarcinoma

Kanlayanee Sawanyawisuth, Ph.D.; Nattawat Tantapotinan; Ratthaphol Kraiklang; Anucha Puapairoj; Chaisiri Wongkham; Gregory J. Riggins; Sopit Wongkham

Annals of Hepatology (Jan 2016)

Suppression of trophoblast cell surface antigen 2 enhances proliferation and migration in liver fluke-associated cholangiocarcinoma

Kanlayanee Sawanyawisuth, Ph.D.,
Nattawat Tantapotinan,
Ratthaphol Kraiklang,
Anucha Puapairoj,
Chaisiri Wongkham,
Gregory J. Riggins,
Sopit Wongkham

Affiliations

Kanlayanee Sawanyawisuth, Ph.D.: Department of Biochemistry, Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; Correspondence and reprint request:
Nattawat Tantapotinan: Department of Biochemistry, Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
Ratthaphol Kraiklang: Department of Biochemistry, Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
Anucha Puapairoj: Department of Pathology, Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
Chaisiri Wongkham: Department of Biochemistry, Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
Gregory J. Riggins: Department of Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, USA
Sopit Wongkham: Department of Biochemistry, Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

Journal volume & issue: Vol. 15, no. 1
pp. 71 – 81

Abstract

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Background and aim. Trophoblast cell surface antigen 2 (TROP2) or tumor-associated calcium signal transducer 2 (TACSTD2) is a 36-kDa type I transmembrane glycoprotein and exerts dual functions as an oncogene and tumor suppressor in cancer cells. In this study, we investigated the expression and functions of TROP2 in liver fluke-associated cholangiocarcinoma (CCA).Material and methods. TROP2 expression in 85 CCA tissues was detected by using immunohistochemistry. The methylation status of TROP2 promoter was studied in 15 matched pairs of normal and CCA formalin fixed paraffin embedded (FFPE) tissues using the bisulfite genomic sequencing (BGS) method. The functions of TROP2 on cancer cell behavior were investigated using siRNA in CCA cell lines. Proliferation, migration and invasion assays were performed. A PCR array was used to evaluate the impact of TROP2 knockdown on the gene expression profiles.Results. TROP2 was highly expressed in all normal bile duct epithelia, but significantly down-regulated in CCA cells. Sixty percent of CCA revealed promoter hypermethylation compared to the corresponding adjacent normal tissues. TROP2 knockdown significantly enhanced the proliferation and migration in CCA cell lines, and altered the expressions of MARCK, EMP1and FILIP1L.Conclusion. We provide new evidence that TROP2 is epigenetically down-regulated and operates as a negative regulator of cell proliferation and migration in liver fluke-associated CCA.

Published in Annals of Hepatology

ISSN: 1665-2681 (Print); 2659-5982 (Online)
Publisher: Elsevier
Country of publisher: Spain
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine
Website: https://www.journals.elsevier.com/annals-of-hepatology

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