title: Proteomic Characterization of Head and Neck Cancer Patient-Derived Xenografts.
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.
  
  
  CONCLUSIONS
  Proteomic characterization of HNSCC PDXs demonstrates potential drivers for model selection and provides a framework for improved utilization of this expanding model system.
authors.affiliation: Department of Otolaryngology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Sarah
authors.initials: S
authors.lastname: Wheeler
authors.affiliation: Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Yongseok
authors.initials: Y
authors.lastname: Park
authors.affiliation: Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Zhenlin
authors.initials: Z
authors.lastname: Ju
authors.affiliation: Departments of Otolaryngology and Cancer Biology, Kansas University Medical Center, Kansas City, Kansas.
authors.forename: Sufi M
authors.initials: SM
authors.lastname: Thomas
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Michele
authors.initials: M
authors.lastname: Fichera
authors.affiliation: Department of Otolaryngology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Egloff
authors.affiliation: Department of Pharmacology and Pharmacy, University of Hong Kong, Hong Kong.
authors.forename: Vivian W
authors.initials: VW
authors.lastname: Lui
authors.affiliation: Department of Otolaryngology, University of Pittsburgh, Pittsburgh, Pennsylvania. Veterans Affairs Pittsburgh Healthcare System, University Drive Campus, Pittsburgh, Pennsylvania.
authors.forename: Umamaheswar
authors.initials: U
authors.lastname: Duvvuri
authors.affiliation: Department of Internal Medicine - Hematology/Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Bauman
authors.affiliation: Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas. Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Mills
authors.affiliation: Department of Otolaryngology, University of Pittsburgh, Pittsburgh, Pennsylvania. Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania. Department of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, California. jennifer.grandis@ucsf.edu.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Grandis
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D016000:Cluster Analysis; D030541:Databases, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism*; D009368:Neoplasm Transplantation; D040901:Proteomics / Q000379:methods*
chemical_list: D009363:Neoplasm Proteins