Coordinated Regulation of Pathways for Enhanced Cell Motility and Chemotaxis Is Conserved in Rat and Mouse Mammary Tumors

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Abstract
Correlating tumor cell behavior in vivo with patterns of gene expression has led to new insights into the microenvironment of tumor cells in the primary tumor. Until now, these studies have been done with cell line–derived tumors. In the current study, we have analyzed, in polyoma middle T oncogene (PyMT)–derived mammary tumors, tumor cell behavior and gene expression patterns of the invasive subpopulation of tumor cells by multiphoton-based intravital imaging and microarray-based expression profiling, respectively. Our results indicate that the patterns of cell behavior that contribute to invasion and metastasis in the PyMT tumor are similar to those seen previously in rat MTLn3 cell line–derived mammary tumors. The invasive tumor cells collected from PyMT mouse mammary tumors, like their counterparts from rat xenograft mammary tumors, are a population that is relatively nondividing and nonapoptotic but chemotherapy resistant and chemotactic. Changes in the expression of genes that occur uniquely in the invasive subpopulation of tumor cells in the PyMT mammary tumors that fall on the Arp2/3 complex, capping protein and cofilin pathways show a pattern like that seen previously in invasive tumor cells from the MTLn3 cell line–derived tumors. These changes predict an enhanced activity of the cofilin pathway, and this was confirmed in isolated invasive PyMT tumor cells. We conclude that changes in gene expression and their related changes in cell behavior, which were identified in the invasive tumor cells of cell line–derived tumors, are conserved in the invasive tumor cells of PyMT-derived mouse mammary tumors, although these tumor types have different genetic origins. [Cancer Res 2007;67(8):1–6]