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

Our plain-English summary of Establishment and histopathological study of patient-derived xenograft models and primary cell lines of epithelioid malignant peritoneal mesothelioma, by Z.R. Yang, Z.G. Chen, Z.H. Ji, et al (Experimental Animals, 2021).

The study

• Authors: Z.R. Yang, Z.G. Chen, Z.H. Ji, Y.L. Lin, J. Zhang, R. Ma, Z. Li, X. Jiang, Q. Chen, X.M. Du, Y. Li
• Journal: Experimental Animals
• Published: 2021;70(2):225-235
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This was a laboratory and animal study from Beijing Shijitan Hospital, China. The authors used surgical tumor tissue from one patient, a 63-year-old woman with malignant peritoneal mesothelioma (a cancer of the abdominal lining). The article reports she had no history of asbestos exposure or smoking. The tumor was grown under the skin of nude mice and passed from mouse to mouse. It was then implanted into the abdomens of 20 mice (10 male, 10 female); cell lines were also grown from it. Tumors formed in all 20 mice, spreading to the pelvic cavity in all 20 and the mesentery in 19. Tumor-spread scores were 8.80 plus or minus 1.75 in female and 9.20 plus or minus 1.81 in male mice (P=0.6219). The mouse tumors and the cultured cells showed features of epithelioid mesothelioma. The mouse tumors stained positive for mesothelioma markers, though more weakly than the patient's tissue. Sequencing found 21 mutated genes shared by models and patient, including BAP1 and NF2. The authors concluded the models offer a platform for studying this cancer. The study did not examine asbestos.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory and animal experiment: patient-derived xenograft (PDX) models in nude mice and primary cell lines, established from one patient's surgical tumor specimen
• Who was studied: Tumor tissue from one 63-year-old female patient with epithelial malignant peritoneal mesothelioma, treated at Beijing Shijitan Hospital, China. The tissue was implanted into the abdomen of 20 BALB/c nude mice (10 male, 10 female).
• Exposure: No asbestos exposure was studied; the source patient had no history of asbestos exposure. The experimental exposure was implantation of the patient's tumor tissue, first under the skin of mice and then, after 4 passages, into the abdominal cavity.
• Main results:
  • Tumors formed in all 20 mice implanted in the abdomen (100%, 20/20).
  • In the 20 mice, tumors invaded the mesentery in 95% (19/20), diaphragm 45% (9/20), liver 50% (10/20), stomach 40% (8/20), pancreas 10% (2/20), spleen 65% (13/20), kidney 40% (8/20) and pelvic cavity 100% (20/20).
  • Experimental peritoneal cancer index (tumor spread) scores were 8.80 plus or minus 1.75 in female mice and 9.20 plus or minus 1.81 in male mice (P=0.6219).
  • Tumors grown under the skin (4th passage) reached 498.31 plus or minus 2.22 cubic millimetres by day 54.
  • The models and primary cell lines showed the features of epithelioid mesothelioma.
  • In the PDX model tumor tissue, Calretinin, Cytokeratin 5/6, WT-1 and Ki-67 staining were all positive.
  • Immunofluorescence staining showed Calretinin and Cytokeratin 5 in the primary cell lines.
  • Sequencing found 26 higher-frequency mutated genes in the PDX models and 36 in the patient. Of these, 21 were shared, including BAP1, NF2, MTBP, NECTIN2, CDC23, LRPPRC, TRIM25 and DHRS2.
  • The shared BAP1 and NF2 mutations had mutation abundances of 99.9% and 90.0%, respectively.
• The authors' conclusion: The authors concluded that the PDX models and primary cell lines reproduce the biological characteristics of malignant peritoneal mesothelioma and provide a platform for laboratory and animal study of the disease.
• Limitations the authors state:
  • Marker staining (Calretinin, Cytokeratin 5/6, WT-1, Ki-67) was stronger in the patient's tumor tissue than in the PDX models' tumor tissue. The authors suggest tumor heterogeneity during passaging as a possible reason.
  • The mutated genes in the models and the patient were not completely identical: 5 were found only in the models and 15 only in the patient.
  • The patient's tissue was sequenced from paraffin sections, while the models' tissue was frozen, which the authors say may have affected the results.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Epithelioid, Peritoneal Mesothelioma, Peritoneal Cancer Index (PCI), Pathology, Mesothelioma, Immunohistochemistry, Calretinin, Cytokeratin 5/6.

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