title: Characterization of the Tumor-Microenvironment in Patient-Derived Cervix Xenografts (OCICx).
abstract: BACKGROUND
  The tumor microenvironment (TME) is heterogeneous including both malignant and host cell components as well as regions of hypoxia, elevated interstitial fluid pressure (IFP) and poor nutrient supply. The quantitative extent to which the microenvironmental properties of primary tumors are recapitulated in xenograft models is not well characterized.
  
  
  METHODS
  Xenografts were generated by implanting tumor biopsies directly into the cervix of mice to create a panel of orthotopically-passaged xenografts (OCICx). Tumors were grown to ~1 cm (diameter) and IFP measurements recorded prior to sacrifice. Enlarged para-aortic lymph nodes (>1-2 mm) were excised for histologic confirmation of metastatic disease. Quantitative histological analysis was used to evaluate hypoxia, proliferation, lymphatic and blood vessels in the epithelial and stromal regions of the xenografts and original patient tumour.
  
  
  RESULTS
  IFP and nodal disease were not correlated with tumor engraftment. IFP measurements in the xenografts were generally lower than those in the patient's tumor. Lymphatic metastasis increased with passage number as did levels of hypoxia in the epithelial component of the xenografts. The blood vessel density in the stromal component of the xenografts increased in parallel. When all the markers were compared between the biopsy and the respective 3rd generation xenograft 10 of 11 tumors showed a good correlation.
  
  
  CONCLUSIONS
  This ongoing study provides characterization about tumoral and stromal heterogeneity in a unique orthotopic xenograft model.
authors.affiliation: Ontario Cancer Institute/Princess Margaret Cancer Centre and Campbell Family Institute for Cancer Research, University Health Network, Toronto, Ontario M5G 2M9, Canada. hill@uhnres.utoronto.ca.
authors.forename: Naz
authors.initials: N
authors.lastname: Chaudary
authors.forename: Melania
authors.initials: M
authors.lastname: Pintilie
authors.forename: Joerg
authors.initials: J
authors.lastname: Schwock
authors.forename: Neesha
authors.initials: N
authors.lastname: Dhani
authors.forename: Blaise
authors.initials: B
authors.lastname: Clarke
authors.forename: Michael
authors.initials: M
authors.lastname: Milosevic
authors.forename: Anthony
authors.initials: A
authors.lastname: Fyles
authors.forename: Richard P
authors.initials: RP
authors.lastname: Hill