Stroma Expression Patterns in Breast Cancer
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: The tissue that forms the stroma surrounding epithelial breast carcinoma cells (tumor microenvironment, TME) is a complex structure that consists of a wide variety of cell types, many of which are poorly described. Recent studies have revealed the importance of the interaction between the TME and tumor cells by showing that the TME actively promotes tumor growth and possibly even metastasis. However, the complexity of the TME makes it difficult to study. For example, it is difficult to determine how the expression patterns of a multitude of different stromal cells vary from one
 
 tumor to the next or to determine to which degree these variances represent distinct stromal signatures. We have developed a novel approach to discover new types of stromal reaction patterns through gene expression profiling of soft tissue tumors (STT). In this approach STTs (that are derived from distinct normal connective tissue precursor cells) function as a “discovery tool” for the various types of stromal reaction patterns. Using this approach and previous CBCRP funding, we have to date described four novel distinct stromal reaction patterns in invasive breast carcinoma. The biological significance of the identification of these various stromal reaction patterns is borne out by the fact that several of these stromal expression patterns have prognostic significance independent from traditional prognosticators such a tumor size, tumor grade and even lymph node status.
 
 
 
 
 
 
 
 The stromal response patterns that we have discovered for breast cancer can be identified in clinical samples through the development of a small panel of antibodies. The current project is focused on stromal responses, or other yet to be discovered stromal responses, present in both invasive cancer and ductal carcinoma in situ (DCIS). Our aims are to: (1) develop clinically useful biomarkers of stromal expression patterns in invasive cancer, and (2) discover stromal response patterns associated with pre-invasive breast cancer. Our experimental approach involves tissue microarrays of 283 cases to screen for antibody markers for different stromal biomarker profiles. We will ultimately reduce each panel down to the best 2-3 markers which will serve as a clinical test for the presence of these stromal signatures in breast cancer. Next, using this data we will analyze a combination of pre-existing DCIS gene expression profiling datasets and generate a novel stromal-based biomarker response profile.
 
 
 
 
 
 
 
 If our research is successful, we will have created clinically practical panels of antibodies that can discriminate key stromal signatures in clinical breast cancer specimens. These panels will have both prognostic utility and may predict response to therapy. Finally, we will have insight into the stromal signatures associated with DCIS, which will assist in clinical decision-making on the best course of therapy.