The goal of this project is to analyze the metastasis of mammary tumors in transgenic mice. This will make use of fluorescently labeled tumor cells to allow in vivo visualization of the tumor cells in the primary tumor as well as in target organs. For the first year of this project we have generated 3 transgenic lines carrying the MMTV-GFP expression construct. We have evaluated GFP fluorescence in one of ...
This final report provides (1) a detailed account of our analysis of the role of the Arp2/3 complex in mediating EGF-stimulated lamellipod extension, (2) a description of our results in producing cell lines expressing talin anti- sense RNA, and (3) a general summary of our understanding of the process of lamellipod extension in mammary adenocarcinoma cells, based upon the work supported by this grant. We find ...
We report upon our studies (1) evaluating the relative roles of lamellipod extension and ruffling in metastatic behavior and (2) developing high resolution methods for localizing important cytoskeletal proteins to the leading edge of EGF-stimulated cells. (1) Addition of E(iF or T&Fa to metastatic NffLn3 cells results in the rapid extension of flat lamellipods. Nonmetastatic MTC cells do not express E&F receptor and show extensive ruffling in even in the ...
Chemotaxis of metastatic MTLn3 cells towards EGF involves the rapid extension of lamellipods. We have characterized extending lamellipods in terms of the location and possible composition of the growth zones. Stimulation of MTLn3 cells with EGF causes a transient increase in actin nucleation activity resulting from the appearance of free barbed ends very close to the leading edge of extending lamellipods. Both actin polymerization and depolymerization are stimulated by EGF. ...
To identify sites at which metastasis of breast cancer cells may be interrupted, we are dissecting the process of cell motility in breast cancer cells. Changes in lamellipod extension and chemotaxis in response to EGF were analyzed forMTLn3 cells (a metastatic cell line derived from the 13762NF rat mammary adenocarcinoma). Addition of EGF produced a cessation of ruffling followed by extension of hyaline lamellipods containing ...
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