Patient-derived xenograft establishment from human malignant pleural mesothelioma

Licun Wu, Ghassan Allo, Thomas John, Ming Li, Tetsuzo Tagawa, Isabelle Opitz, Masaki Anraku, Zhihong Yun, Melania Pintilie, Bethany Pitcher, Geoffrey Liu, Ron Feld, Michael R. Johnston, Marc De Perrot, Ming Sound Tsao

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Purpose: Malignant pleural mesothelioma (MPM) is a rare but aggressive disease with few therapeutic options. The tumor-stromal interface is important in MPM, but this is lost in cell lines, the main model used for preclinical studies. We sought to characterize MPM patient-derived xenografts (PDX) to determine their suitability as preclinical models and whether tumors that engraft reflect a more aggressive biological phenotype. Experimental Design: Fresh tumors were harvested from extrapleural pneumonectomy, decortication, or biopsy samples of 50 MPM patients and implanted subcutaneously into immunodeficient mice and serially passaged for up to five generations. We correlated selected mesothelioma biomarkers between PDX and patient tumors, and PDX establishment with the clinical pathologic features of the patients, including their survival. DNA of nine PDXs was profiled using the OncoScan FFPE Express platform. Ten PDXs were treated with cisplatin and pemetrexed. Results: A PDX was formed in 20 of 50 (40%) tumors implanted. Histologically, PDX models closely resembled the parent tumor. PDX models formed despite preoperative chemotherapy and radiotherapy. In multivariable analysis, patients whose tumors formed a PDX had significantly poorer survival when the model was adjusted for preoperative treatment (HR, 2.46; 95% confidence interval, 1.1- 5.52; P = 0.028). Among 10 models treated with cisplatin, seven demonstrated growth inhibition. Genomic abnormalities seen in nine PDX models were similar to that previously reported. Conclusions: Patients whose tumors form PDX models have poorer clinical outcomes. MPM PDX tumors closely resemble the genotype and phenotype of parent tumors, making them valuable models for preclinical studies.

Original languageEnglish
Pages (from-to)1060-1067
Number of pages8
JournalClinical Cancer Research
Volume23
Issue number4
DOIs
Publication statusPublished - Feb 15 2017
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Patient-derived xenograft establishment from human malignant pleural mesothelioma'. Together they form a unique fingerprint.

  • Cite this

    Wu, L., Allo, G., John, T., Li, M., Tagawa, T., Opitz, I., Anraku, M., Yun, Z., Pintilie, M., Pitcher, B., Liu, G., Feld, R., Johnston, M. R., De Perrot, M., & Tsao, M. S. (2017). Patient-derived xenograft establishment from human malignant pleural mesothelioma. Clinical Cancer Research, 23(4), 1060-1067. https://doi.org/10.1158/1078-0432.CCR-16-0844