title: Tumor grafts derived from patients with head and neck squamous carcinoma authentically maintain the molecular and histologic characteristics of human cancers.
abstract: BACKGROUND
  The patient-derived xenograft (PDX) model is likely to reflect human tumor biology more accurately than cultured cell lines because human tumors are implanted directly into animals; maintained in an in vivo, three-dimensional environment; and never cultured on plastic. PDX models of head and neck squamous cell carcinoma (HNSCC) have been developed previously but were not well characterized at the molecular level. HNSCC is a deadly and disfiguring disease for which better systemic therapy is desperately needed. The development of new therapies and the understanding of HNSCC biology both depend upon clinically relevant animal models. We developed and characterized the patient-derived xenograft (PDX) model because it is likely to recapitulate human tumor biology.
  
  
  METHODS
  We transplanted 30 primary tumors directly into mice. The histology and stromal components were analyzed by immunohistochemistry. Gene expression analysis was conducted on patient tumors and on PDXs and cell lines derived from one PDX and from independent, human tumors.
  
  
  RESULTS
  Five of 30 (17%) transplanted tumors could be serially passaged. Engraftment was more frequent among HNSCC with poor differentiation and nodal disease. The tumors maintained the histologic characteristics of the parent tumor, although human stromal components were lost upon engraftment. The degree of difference in gene expression between the PDX and its parent tumor varied widely but was stable up to the tenth generation in one PDX. For genes whose expression differed between parent tumors and cell lines in culture, the PDX expression pattern was very similar to that of the parent tumor. There were also significant expression differences between the human tumors that subsequently grew in mice and those that did not, suggesting that this model enriches for cancers with distinct biological features. The PDX model was used successfully to test targeted drugs in vivo.
  
  
  CONCLUSIONS
  The PDX model for HNSCC is feasible, recapitulates the histology of the original tumor, and generates stable gene expression patterns. Gene expression patterns and histology suggested that the PDX more closely recapitulated the parental tumor than did cells in culture. Thus, the PDX is a robust model in which to evaluate tumor biology and novel therapeutics.
authors: Departments of Thoracic/Head and Neck Medical Oncology, Unit 432, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston 77030-4009, TX, USA. fmjohns@mdanderson.org.
authors: Shaohua
authors: S
authors: Peng
authors: Chad J
authors: CJ
authors: Creighton
authors: Yiqun
authors: Y
authors: Zhang
authors: Banibrata
authors: B
authors: Sen
authors: Tuhina
authors: T
authors: Mazumdar
authors: Jeffery N
authors: JN
authors: Myers
authors: Stephen Y
authors: SY
authors: Lai
authors: Adrian
authors: A
authors: Woolfson
authors: Matthew V
authors: MV
authors: Lorenzi
authors: Diana
authors: D
authors: Bell
authors: Michelle D
authors: MD
authors: Williams
authors: Faye M
authors: FM
authors: Johnson
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000077195:Squamous Cell Carcinoma of Head and Neck; D017154:Stromal Cells / Q000473:pathology; D023041:Xenograft Model Antitumor Assays; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D053612:Janus Kinases; D019061:src-Family Kinases
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