Coordinated regulation of pathways for enhanced cell motility and chemotaxis is conserved in rat and mouse mammary tumors Free

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Correlating tumor cell behavior in vivo with patterns of gene expression has lead to new insights into the microenvironment of tumor cells in the primary tumor and the molecular mechanisms behind tumor cell behavior during metastasis. In the current study, in Polyoma middle T oncogene (PyMT) derived mammary tumors, tumor cell behavior and gene expression patterns of the invasive subpopulation of tumor cells were analyzed by intravital imaging and microarray-based 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 non dividing and non apoptotic 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 similar pattern of change to 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 tumor cells. We conclude that changes in cell behavior, and the consequences of changes in gene expression, that were identified in the invasive tumor cells of MTLn3 rat tumors, are conserved in the invasive tumor cells of PyMT derived mouse mammary tumors.