Project: Research project

Project Details


DESCRIPTION: (Applicant's Description)
We propose to develop clinically relevant mouse models that resemble human
breast tumors in etiology and histology. We propose to use these mouse models
to procure pure populations of motile and invasive tumor cells from primary
tumors in live intact mice under direct visualization using novel imaging
technology. We propose to develop high sensitivity DNA microarrays for use
with these cells so as to examine gene expression patterns unique to the
invasive and metastatic population of cells in the primary tumor compared to
other populations of tumor and normal cells. The coupling of cell behavior to
gene expression will allow the rational interpretation of gene expression
patterns in metastatic tumors.

The specific aims for the R21 phase of the project are:
1. Prepare mouse models that develop metastatic breast tumors as seen in
patients and that can be used for imaging of tumor cell behavior in vivo
by multi-photon microscopy.
2. Develop methods for multi-photon imaging of normal and tumor bearing
mouse mammary glands.
3. Refine methods for collecting chemotactic cells from the primary tumor
that have been characterized by direct imaging and that represent the
population of cells capable of chemotaxis to vessels and surrounding
tissue in response to serum and growth factors.

The specific aims for the R33 phase of the project are:
1. Develop sensitive DNA microarray techniques for comparing small numbers
of chemotactic tumor cells and white cells collected from the primary
tumor with tumor cells and white cells collected from elsewhere.
2. Demonstrate the utility of comparing gene expression patterns of 8
categories of cells collected from various mouse models to identify
patterns unique to different subpopulations of cells.
3. Develop methods to correlate the gene expression patterns of cells
collected with microneedles from the primary tumor with the histology
and behavioral phenotypes of cells at the collection sites.
4. Evaluate a variety of clustering algorithms, with DNA expression
patterns obtained in specific aims 2 and 3, to identify genes related to
cell behaviors believed necessary for metastasis.
Effective start/end date2/14/011/31/02


  • National Cancer Institute: $167,500.00


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