Differential Gene expression profile in breast cancer-derived stromal fibroblasts

1. Background:

Breast cancer is chatacterized by malignant transformation of epithelial cells, but stromal cells also play an important role in tumorigenesis. While tumoral fibroblasts display unique phenotypical properties, it is unclear whether they also represent are a specific subpopulation.

2. Materials and Methods:

Stromal fibroblasts deriving from malignant tissue of 10 women with invasive breast cancer, and from normal breast tissue of 10 women with benign breast disorders, were subjected to differential complementary DNA Microarray Analysis by using a 2400 gene cDNA array. Gene expression results were validated by immunohistochemistry.

3. Results:

In a cDNA Array that allows to analyze the differential gene expression of more than 2400 genes, the mRNA expression of 135 genes were increased more than 2 fold in fibroblasts from malignant breast tumors. The majority of these genes encode tumor-promoting cytokines, transcription factors and cell-matrix associated proteins. The mRNA expression of 110 genes decreased to less than 0.5 fold. The remaining 2155 genes were not significantly altered. Immunohistochemistry for selected proteins performed on biopsies from breast cancer and normal breast tissues confirmed the clinical relevance of our findings.

4. Conclusion:

Breast cancer-derived stromal fibroblasts show a distinctive gene expression pattern that differentiates them from normal breast stroma. Our observation of increased expression of tumor promotion-associated genes even in the absence of adjacent malignant epithelium suggests that tumor stroma is comprised of a fibroblastic subpopulation that provides for a microenvironment which supports tumor growth and invasion.