Abstract 1488: Metastatic analysis of clonal epithelial and mesenchymal-like murine mammary tumor cells.

Abstract Tumor metastasis is the most common cause of cancer mortality, and yet it is among the most poorly understood processes in tumor progression. While carcinomas are composed primarily of epithelial cells, tumors contain a continuum of cells with epithelial and mesenchymal-like properties. This tumor cell heterogeneity is attributed to differentiation plasticity, which is characterized by epithelial to mesenchymal (EMT) or mesenchymal to epithelial transitions (MET). It has been proposed that tumor cells undergo EMT in order to disseminate from the primary tumor and MET in order to seed at secondary sites. The invasive mesenchymal carcinoma cell phenotype is thought to be a state required for tumor dissemination, but to date, pathologists have not found conclusive evidence of mesenchymal cells in human metastatic tumor samples. An alternative theory suggests that both mesenchymal and epithelial cells are required for metastasis to occur. According to this theory, detachment from the primary tumor and invasion by mesenchymal cells facilitates the movement of epithelial tumor cells that are able to seed at distant sites. We hypothesize that the presence of mesenchymal-like mammary tumor cells facilitate the metastasis of epithelial tumor cells and that only epithelial cells are able to seed at distant sites. To test this hypothesis, we cloned epithelial and mesenchymal-like primary cell lines from spontaneous mammary tumors produced in FVB MMTV/Neu mice. Epithelial cells have been stably transfected to express firefly luciferase and GFP, and we are in the process of cloning mesenchymal-like cells expressing Renilla luciferase and mCherry. We have preliminary data that shows that when clonal epithelial cells are administered into the mammary fat pad of FVB MMTV/Neu mice, tumors grow, but do not form metastatic lesions. In contrast, when stably transfected clonal epithelial cells are administered with non-transfected clonal mesenchymal-like tumor cells, luciferase+ metastatic lesions in the spleen, liver and lung are detected biophotonically, and GFP + cells are detected in the spleen and liver. These data indicate that epithelial cells are present (but does not rule out the presence of mesenchymal cells) at the metastatic site. Whether epithelial cells undergo EMT, and how metastasis is facilitated by the presence of mesenchymal cells remains to be determined. Citation Format: Katie A. Palen, Bryon D. Johnson, Jill A. Gershan. Metastatic analysis of clonal epithelial and mesenchymal-like murine mammary tumor cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1488. doi:10.1158/1538-7445.AM2013-1488