Establishment of Patient-derived Preclinical Models for Invasive Papillary Cholangiocarcinoma

  • Anticancer Res. 2022 Jan;42(1):599-608. doi: 10.21873/anticanres.15517.
Benjamin Mwesige  1  2 ,  Mi Rim Lee  1  2 ,  Yu-Sun Lee  2  3 ,  Na Young Han  4 ,  Ji Eun Im  2 ,  Joon-Ki Kim  2 ,  Sun Il Choi  2 ,  En Kyung Hong  4 ,  A-Ra Jeon  2 ,  Sang-Jae Park  5 ,  Sang Myung Woo  6  5 ,  Yun-Hee Kim  6  2
Affiliations
  • 1. Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Republic of Korea.
  • 2. Division of Convergence Technology, Research Institute of National Cancer Center, Goyang, Republic of Korea.
  • 3. Department of Basic Biomedical, Kyung Hee University, Seoul, Republic of Korea.
  • 4. Department of Pathology, National Cancer Center, Goyang, Republic of Korea.
  • 5. Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Republic of Korea.
  • 6. Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Republic of Korea [email protected] [email protected].
PMID: 34969769 DOI: 10.21873/anticanres.15517
Abstract

Background/aim: Invasive papillary cholangio-carcinoma (IPC) is a minor subtype of extrahepatic cholangiocarcinoma. However, its etiology and characteristics remain unknown because of the unavailability of in vitro and in vivo models. We aimed to establish a novel preclinical model for translational research of IPC.

Materials and methods: A patient-derived xenograft (PDX) was engrafted in NOG mice and the cell line National Cancer Center human IPC (NCChIPC) was subsequently established from the PDX tumors. Immunohistochemistry and RNA-sequencing were used to determine the retention of original characteristics of patient tissues.

Results: PDX tumors showed successful amplification, and the NCChIPC-derived xenograft largely retained the histopathological features of the original tumor with CK19, MUC1 and MUC5AC expression. Transcriptome analysis showed a high correlation between patient and preclinical models. Additionally, Anticancer drugs response was analyzed in the NCChIPC PDX.

Conclusion: These novel preclinical models here will help elucidate IPC etiology and facilitate translational research.

Keywords
Invasive papillary cholangiocarcinoma; patient-derived xenograft; preclinical model.
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