Establishment and histopathological study of patient-derived xenograft models and primary cell lines of epithelioid malignant peritoneal mesothelioma

Zhi-Ran Yang; Zhi-Gao Chen; Zhong-He Ji; Yu-Lin Lin; Jue Zhang; Ru Ma; Zhao Li; Xi Jiang; Qian Chen; Xue-Mei Du; Yan Li

doi:10.1538/expanim.20-0119

Original

Establishment and histopathological study of patient-derived xenograft models and primary cell lines of epithelioid malignant peritoneal mesothelioma

Zhi-Ran Yang, Zhi-Gao Chen, Zhong-He Ji, Yu-Lin Lin, Jue Zhang, Ru Ma, Zhao Li, Xi Jiang, Qian Chen, Xue-Mei Du, Yan Li

Author information

Zhi-Ran Yang
Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, No. 10 Tieyi Road, Yangfangdian Street, Haidian District, Beijing 100038, China
Zhi-Gao Chen
Thorgene Co., Ltd., Yizhuang Biomedical Park, Daxing District, Beijing, Beijing, China
Zhong-He Ji
Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, No. 10 Tieyi Road, Yangfangdian Street, Haidian District, Beijing 100038, China
Yu-Lin Lin
Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, No. 10 Tieyi Road, Yangfangdian Street, Haidian District, Beijing 100038, China
Jue Zhang
Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, No. 10 Tieyi Road, Yangfangdian Street, Haidian District, Beijing 100038, China
Ru Ma
Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, No. 10 Tieyi Road, Yangfangdian Street, Haidian District, Beijing 100038, China
Zhao Li
Department of Pathology, Beijing Shijitan Hospital, Capital Medical University, Capital Medical University, No. 10 Tieyi Road, Yangfangdian Street, Haidian District, Beijing, China
Xi Jiang
Department of Pathology, Beijing Shijitan Hospital, Capital Medical University, Capital Medical University, No. 10 Tieyi Road, Yangfangdian Street, Haidian District, Beijing, China
Qian Chen
Thorgene Co., Ltd., Yizhuang Biomedical Park, Daxing District, Beijing, Beijing, China
Xue-Mei Du
Department of Pathology, Beijing Shijitan Hospital, Capital Medical University, Capital Medical University, No. 10 Tieyi Road, Yangfangdian Street, Haidian District, Beijing, China
Yan Li
Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, No. 10 Tieyi Road, Yangfangdian Street, Haidian District, Beijing 100038, China
Department of Pathology, Beijing Shijitan Hospital, Capital Medical University, Capital Medical University, No. 10 Tieyi Road, Yangfangdian Street, Haidian District, Beijing, China

Keywords: histopathological study, malignant peritoneal mesothelioma, patient-derived xenograft (PDX) model, primary cell lines, whole exome sequencing

JOURNAL OPEN ACCESS

2021 Volume 70 Issue 2 Pages 225-235

DOI https://doi.org/10.1538/expanim.20-0119

Browse “Advance online publication” version

Details

Abstract

Malignant peritoneal mesothelioma (MPM) is a rare malignancy with few experimental models. This study used the human surgical specimen to establish MPM patient-derived xenograft (PDX) models and primary cell lines to provide a study platform for MPM in vitro and in vivo, and conducted histopathological analysis. Our study used the experimental peritoneal cancer index (ePCI) score to evaluate gross pathology, and the results showed that the ePCI score of the female and male nude mice were 8.80 ± 1.75 and 9.20 ± 1.81 (P=0.6219), respectively. The Hematoxylin and eosin (HE) staining of animal models showed that the tumor was epithelioid mesothelioma and invaded multiple organs. Immunohistochemistry (IHC) staining showed that Calretinin, Cytokeratin 5/6, WT-1 and Ki-67 were all positive. The Swiss-Giemsa and Immunofluorescence (IF) staining of primary cell lines were also consistent with the pathological characteristics of mesothelioma. We also performed the whole-exome sequencing (WES) to identify the mutant genes between models and the patient. And the results showed that 21 mutant genes were shared between the two groups, and the genes related to tumorigenesis and development including BAP1, NF2, MTBP, NECTIN2, CDC23, LRPPRC, TRIM25, and DHRS2. In conclusion, the PDX models and primary cell lines of MPM were successfully established with the epithelioid mesothelioma identity confirmed by histopathological evidence. Moreover, our study has also illustrated the shared genomic profile between models and the patient.

Corresponding author

Register with J-STAGE for free!