In vitro Characterization of a novel murine model of cancerous progression

Abstract

To evaluate a potentially valuable tool to study cancer progression and metastasis, we characterized a novel murine model composed of a parental oncogene-transformed embryonic fibroblast line and five cell lines isolated from progressively advanced tumors. Lines derived from distant metastases displayed significantly greater rates of motility, invasiveness, and extracellular acidification than lines derived from a primary tumor or local metastases. A comprehensive proteomic analysis of these cells showed numerous oncogenes to be upregulated and tumor suppressors to be downregulated in the advanced lines, and provided novel targets for future examination. The first cell line capable of extravasation displayed particularly high proteomic variation, which could provide insight into its epithelial to mesenchymal transition. The proteomic variation was less than that of an established human breast cancer model, indicating that the observed differences are more likely contributive to tumorigenesis. In total, we validated a novel cell model for the study of tumorigenesis, while providing a robust proteomic data set to guide future research.