Proteomic characterization of head and neck cancer patient-derived xenografts

Hua Li, Sarah Wheeler, Yongseok Park, Zhenlin Ju, Sufi M. Thomas, Michele Fichera, Ann M. Egloff, Vivian W. Lui, Umamaheswar Duvvuri, Julie E. Bauman, Gordon Mills, Jennifer R. Grandis

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Despite advances in treatment approaches for head and neck squamous cell carcinoma (HNSCC), survival rates have remained stagnant due to the paucity of preclinical models that accurately reflect the human tumor. Patient-derived xenografts (PDX) are an emerging model system where patient tumors are implanted directly into mice. Increased understanding of the application and limitations of PDXs will facilitate their rational use. Studies to date have not reported protein profiles of PDXs. Therefore, we developed a large cohort of HNSCC PDXs and found that tumor take rate was not influenced by the clinical, pathologic, or processing features. Protein expression profiles, from a subset of the PDXs, were characterized by reverse-phase protein array and the data was compared with The Cancer Genome Atlas HNSCC data. Cluster analysis revealed that HNSCC PDXs were more similar to primary HNSCC than to any other tumor type. Interestingly, while a significant fraction of proteins were expressed similarly in both primary HNSCC and PDXs, a subset of proteins/phosphoproteins were expressed at higher (or lower) levels in PDXs compared with primary HNSCC. These findings indicate that the proteome is generally conserved in PDXs, but mechanisms for both positive and negative model selection and/or differences in the stromal components exist. Implications: Proteomic characterization of HNSCC PDXs demonstrates potential drivers for model selection and provides a framework for improved utilization of this expanding model system.

Original languageEnglish (US)
Pages (from-to)278-286
Number of pages9
JournalMolecular Cancer Research
Volume14
Issue number3
DOIs
Publication statusPublished - Mar 1 2016
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

Cite this

Li, H., Wheeler, S., Park, Y., Ju, Z., Thomas, S. M., Fichera, M., ... Grandis, J. R. (2016). Proteomic characterization of head and neck cancer patient-derived xenografts. Molecular Cancer Research, 14(3), 278-286. https://doi.org/10.1158/1541-7786.MCR-15-0354