CD36 repression activates a multicellular stromal program shared by high mammographic density and tumor tissues.
Rosa Anna DeFilippis1, Hang Chang, Nancy Dumont
1Department of Pathology, Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94143, USA.
Cancer Discovery
|July 11, 2012
Summary
CD36 repression is linked to high mammographic density and breast cancer. This transmembrane receptor controls adipocyte and extracellular matrix content, offering potential therapeutic targets for intervention.
Area of Science:
- Oncology
- Molecular Biology
- Radiology
Background:
- High mammographic density is a significant risk factor for invasive breast cancer.
- The genetic factors influencing mammographic density remain largely unknown.
- High-density tissues share stromal characteristics with tumors, including low adipocyte and high extracellular matrix (ECM) content.
Purpose of the Study:
- To identify genes modulating mammographic density.
- To investigate the role of CD36 in high mammographic density and tumor stroma.
Main Methods:
- In vitro and in vivo assays were employed.
- Expression levels of CD36 were analyzed in disease-free stroma associated with high mammographic density and tumor stroma.
- Functional assays assessed the impact of CD36 repression on adipocyte differentiation, angiogenesis, cell-ECM interactions, and immune signaling.
Main Results:
- CD36 is significantly repressed in stromal cells of high mammographic density and tumor tissues.
- CD36 repression was found to be necessary and sufficient to induce phenotypes characteristic of high mammographic density and tumor stroma.
- CD36 expression levels correlated strongly with clinical outcomes.
Conclusions:
- CD36 coordinates adipocyte content and matrix accumulation, and its repression in stromal cells is an early event in tumorigenesis.
- Both CD36 levels and mammographic density are modifiable factors, suggesting potential for therapeutic intervention.
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