Abstract 4198: Characterization of basal cell carcinoma (BCC) allograft in comparison with spontaneous murine BCCs

Abstract

Abstract Small molecule inhibitors against Hedgehog (HH) activity have become one of the hottest targets in cancer drug development. This is because HH pathway has been found to play a role in possibly as many as 30% of all human malignancies, including basal cell carcinoma (BCC), medulloblastoma, rhabdomyosarcoma, pancreatic, gastrointestinal, ovarian, and prostate cancers, some leukemias, and multiple myeloma. Ptch 1+/− mice develop BCCs after UV or ionizing radiation and provide an excellent model system for investigating the HH regulatory system, studying the effect of HH in cancer biology, and evaluating tumor intervention therapies. However, there are intrinsic limitations to the use of autochthonous mouse tumors to investigate therapeutic interventions, including inter-tumor variability and long tumor latency, necessitating the enrolling of numerous mice to assess the efficacy of any intervention. One approach to circumventing these problems is to use tumor allografts. In the present study we aimed to develop BCC tumor allografts, which have not previously been established successfully, and to compare their histology, growth rate, vasculature, and sensitivity to drug treatment with that of their parental tumors. We injected single cell suspensions derived from primary murine BCCs into multiple NOD/SCID mice and compared allograft histology (H&E) and immunophenotype (Ki67, Gli1 and CD31) with that of the parental tumors. We found that allografts generated from the same spontaneous tumor were relatively similar to one another and reproduced the histology of the parental tumor, exhibiting either an infiltrative subtype or a nested structure resembling infiltrative/trichoepithelioma or nodular human BCC subtypes respectively. Consistent with their faster growth rate, allograft tumors showed greater Ki67 staining than did primary tumors. However, allografts expressed slightly reduced Gli1 levels. Similar vascular distribution was observed in both tumor models. Finally, we tested the tumor allograft sensitivity to HH inhibitor treatments. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4198.