The majority of cancer patients die from tumor relapse. Consequently, characteristics of tumor cells that may contribute to aggressive cancer progression are under intense investigation. Tumors are composed of heterogeneous populations of cells that express a continuum of epithelial and mesenchymal markers. There is mounting evidence that mesenchymal tumor cells acquire invasive features and are refractory to conventional treatment, but in order to decipher the contribution of both epithelial and mesenchymal-like tumor cells to disease relapse we must understand the cellular and molecular properties of each cell type. Using a combination of different culture conditions and cell sorting strategies, we cloned epithelial and mesenchymal-like tumor cells that were derived from FVB Tg MMTV/Neu spontaneous mammary tumors. The availability of these clonal primary cell lines provides an unique opportunity to compare tumor cell properties that may contribute to aggressive disease such as proliferation, resistance to apoptosis, tumorigenicity, invasiveness, expression of growth factor and cytokine receptors, inflammatory cytokine secretion, immunogenicity, and expression or down-regulation of immune-modulatory molecules. Some of our preliminary data has revealed that (1) Epithelial cells are more proliferative in vitro, and cell proliferation was reduced upon exposure to the tyrosine kinase inhibitor, TKI-258. TKI-258 did not significantly decrease the proliferation of mesenchymal-like tumor cells, (2) A population of epithelial-enriched cells was more tumorigenic as compared to mesenchymal-like-enriched cells when administered to an immune competent syngeneic host, (3) Epithelial cells express greater Neu transgene, IL-6 and TNF-α transcripts than mesenchymal-like cells, and (4) When low passage clonal epithelial and mesenchymal-like cells were used as a whole cell tumor vaccine in FVB wild-type mice there was an increase in CD8 T cell activation as compared to that elicited by administration of a non-clonal high passage tumor cell line. We are continuing to explore molecular and functional differences between the clonal epithelial, clonal mesenchymal and the non-clonal tumor cell line cells. Characterization of epithelial and mesenchymal-like tumor cells represents an initial step in deciphering how tumor cells contribute to aggressive cancer progression and will offer insight into how epithelial and mesenchymal-like tumor cells respond to therapeutic interventions. The ultimate goal will be to tailor anticancer therapy toward eradicating the unique type of tumor cells that populate patient tumors.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 327. doi:1538-7445.AM2012-327