Abstract 5136: The Flint Animal Cancer Center (FACC) canine tumor cell line panel: A resource for comparative and translational oncology

Abstract

Abstract Purpose: Mammalian cell tissue culture has been a critical tool leading to our current understanding of cancer including many aspects of cellular transformation, growth, and response to therapies. The current use of large panels of human cancer cell lines (i.e. NCI60, GDSC) with associated phenotypic and genotypic information allows for informatics approaches and in silico screens to rapidly test hypotheses based on simple as well as complex relationships. We have assembled a panel of canine cancer cell lines to facilitate translational studies in canine cancer and report here the characteristics and some applications of this panel in comparative oncology. Methods: Canine cancer cell lines isolated from tumors have been accumulated from a number of sources over the years. Our current panel consists of 29 cell lines that have been validated as being of canine origin and “fingerprinted” by microsatellite analysis. The tumor types represented include 10 osteosarcomas, 5 melanomas, 2 mammary carcinomas, 1 hemangiosarcoma, 2 bladder carcinomas, 4 lymphoma/leukemias, 1 mast cell tumor, 2 histiocytic sarcomas, 1 thyroid carcinoma and 1 soft-tissue sarcoma. Drug sensitivity analysis was carried out using a resazurin-based bioreductive fluorometric assay. Gene expression microarray analysis was carried out using the Affymetrix GeneChip Canine 2.0 at the Genomics and Microarray Core (University of Colorado Cancer Center). Results: Drug sensitivity to the cytotoxic chemotherapeutic agents carboplatin, cisplatin, doxorubicin, lomustine, paclitaxel and vinblastine were assessed and compared to responses in the human NCI-60 panel. Results show that the human and canine cell lines show similar ranges of sensitivity to these agents. The mean GI50 values for the human and canine cell lines are significantly different for DOX, VBL, CARBO, CCNU as well as PTX. The variances in the data were also significantly different for CARBO and PTX. Overall, however, the drug sensitivity/resistance patterns in the canine and human tumor cell line panels shared general trends with regard to sensitivity and variance observed to the specific agents with the mean Log GI50 values for each agent showing a cross-species correlation (r = 0.88, p = 0.0194, Pearson). Cluster analysis of the gene expression data using the top 100 most variant genes as well as the 100 top most variant cancer genes largely separates the panel into groups with similar histiotypes. Cluster analysis of cancer genes also highlights alterations in gene expression that may contribute to pathogenesis in some cell lines such as loss of the PTEN tumor suppressor or elevated expression of receptor tyrosine kinase genes. Conclusions: The FACC canine tumor cell line panel represents a validated panel of representative cancers from dogs that can be utilized for comparative oncology studies as well as applications in drug development where use of a companion animal model is appropriate. Citation Format: Daniel L. Gustafson, Jared S. Fowles, Douglas H. Thamm, Rodney L. Page, Dawn L. Duval. The Flint Animal Cancer Center (FACC) canine tumor cell line panel: A resource for comparative and translational oncology. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5136. doi:10.1158/1538-7445.AM2015-5136