We have developed state-of-the-art methods necessary to observe tumor cell invasion and intravasation directly in rat and mouse mammary tumors, correlate these cell behaviors with metastatic potential and connect these behaviors to the gene expression patterns seen in the migratory and invasive subpopulation of mammary tumor cells in the primary tumor. Furthermore, these methods can be used to characterize microenvironments that cause autocrine and paracrine-mediated cell migration resulting in the accumulation of cells around an initiating chemotactic signal, sometimes associated with blood vessels. This raises the exciting possibility that there exist self-propagating autocrine and paracrine loops that are tumor grade specific and that operate in the primary tumor, and possibly secondary and tertiary metastatic tumors, giving rise to systemic invasion and metastasis. Extension of this new technology to human breast tumors will allow us to explore the variety of stromal cells and microenvironments in this heterogeneous human tumor that are involved in invasion and metastasis, and determine if a cohort of gene expression changes exists as a common invasion signature that may have prognostic and therapeutic value.
The specific aims of the proposal are: 1. Identify microenvironments involved in invasion in human breast tumors. 2. Determine gene expression profiles of invasive cells in human breast tumors.
|Rodriguez-Tirado, Carolina; Kitamura, Takanori; Kato, Yu et al. (2016) Long-term High-Resolution Intravital Microscopy in the Lung with a Vacuum Stabilized Imaging Window. J Vis Exp :|
|Kwon, Mijung; Lee, Soo Jin; Wang, Yarong et al. (2014) Filamin A interacting protein 1-like inhibits WNT signaling and MMP expression to suppress cancer cell invasion and metastasis. Int J Cancer 135:48-60|
|Gertler, Frank; Condeelis, John (2011) Metastasis: tumor cells becoming MENAcing. Trends Cell Biol 21:81-90|
|Oser, Matthew; Dovas, Athanassios; Cox, Dianne et al. (2011) Nck1 and Grb2 localization patterns can distinguish invadopodia from podosomes. Eur J Cell Biol 90:181-8|
|Roussos, Evanthia T; Condeelis, John S; Patsialou, Antonia (2011) Chemotaxis in cancer. Nat Rev Cancer 11:573-87|
|Wyckoff, Jeffrey; Gligorijevic, Bojana; Entenberg, David et al. (2011) The in vivo invasion assay: preparation and handling of collection needles. Cold Spring Harb Protoc 2011:1232-4|
|Wyckoff, Jeffrey; Gligorijevic, Bojana; Entenberg, David et al. (2011) High-resolution multiphoton imaging of tumors in vivo. Cold Spring Harb Protoc 2011:1167-84|
|Mader, Christopher C; Oser, Matthew; Magalhaes, Marco A O et al. (2011) An EGFR-Src-Arg-cortactin pathway mediates functional maturation of invadopodia and breast cancer cell invasion. Cancer Res 71:1730-41|
|Roussos, Evanthia T; Goswami, Sumanta; Balsamo, Michele et al. (2011) Mena invasive (Mena(INV)) and Mena11a isoforms play distinct roles in breast cancer cell cohesion and association with TMEM. Clin Exp Metastasis 28:515-27|
|Roussos, Evanthia T; Wang, Yarong; Wyckoff, Jeffrey B et al. (2010) Mena deficiency delays tumor progression and decreases metastasis in polyoma middle-T transgenic mouse mammary tumors. Breast Cancer Res 12:R101|
Showing the most recent 10 out of 19 publications