Gene activity in breast stromal cells can be important in stimulating growth of ductal carcinoma cells, suggesting that new treatments targeting both cancer cells and abnormal stromal cells may be more effective than existing therapies, according to an article in the July 20th issue of Cancer Cell.

Before they could study gene activity in breast cells and make an expression profile of each gene, the researchers first needed to make very pure samples of each of six cell types in breast tissue specimens. (These were taken from women without cancer undergoing breast reduction surgery, as well as from women with ductal carcinoma in situ or invasive breast cancer.)

SAGE (serial analysis of gene expression) was used to measure the level of expression of each gene in the different cell types. These activity profiles changed depending on whether the cells were from a normal specimen or were from carcinoma in situ or invasive cancer.

From the genes’ activity in tissues of different types, the scientists were able to deduce which ones were involved in carcinogenesis or progression of cancer. Some of the genes were previously unknown. In other instances, the genes were known but their involvement in breast cancer hadn’t been recognized.

After a comprehensive gene expression survey of ductal carcinoma cells (from invasive and in situ tumors) and stromal cells, the American research team singled out two genes in stromal cells as potential targets for therapy. The genes, CXCL12 and CXCL14, encode chemokines that can prompt cancer progression.

One potential benefit of the new gene survey could be a way to detect a gene activity “signature” in ductal carcinoma in situ cells to predict how likely they are to progress to invasive cancer. Such a test, not available now, might save some women from needlessly aggressive treatment.

“By finding factors released by surrounding stromal cells that support the growth of the tumor and targeting these components with cancer drugs, it might be more effective than targeting the tumor cells alone,” said Kornelia Polyak, MD, PhD, the study’s senior author. The only current therapy that targets the stroma is antiangiogenic agents, which are intended to disrupt the blood supply to growing tumors.