Characterization of the Tumor-Microenvironment in Patient-Derived Cervix Xenografts (OCICx)

Abstract

<em>Rationale</em>: 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. <em>Methods</em>: 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. <em>Results</em>: 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. <em>Conclusions</em>: This ongoing study provides characterization about tumoral and stromal heterogeneity in a unique orthotopic xenograft model.

Keywords

• cervix cancer
• stroma
• patient-derived cervix xenograft
• hypoxia
• tumor microenvironment