Researcher eavesdrops on 'molecular dialogue' in breast cancer
Kornelia Polyak, MD, PhD, is shedding light on the interaction between breast cancer cells and noncancerous cells surrounding them.
What hard evidence is there that the microenvironment has an impact on cancer?
Consider this: Some laboratory tests suggest that when cancer cells are placed within normal, healthy tissue, they become normal.
For Dana-Farber's Kornelia Polyak, MD, PhD, the microenvironment's role in a certain form of breast cancer is vividly clear. While studying a cancerous condition called ductal carcinoma in situ (DCIS), she noticed that gene activity patterns in DCIS cells were essentially the same whether the cells were confined to the milk ducts of the breast or had invaded other parts of the body. The cause of their differing behavior, she reasoned, may lie in the noncancerous cells that surround tumor cells in the lining of the ducts, an area called the epithelium.
When she and her colleagues used normal and DCIS tissue to analyze the epithelial and nearby myoepithelial cells, as well as cells in enveloping tissue called stroma, they found unusually high levels of gene activity in DCIS tissue. The revved-up genes in DCIS prompt the microenvironment to signal tumor cells to grow faster and become more aggressive. "We developed a line of cells in the laboratory that look and behave like DCIS. When we mixed them with stromal cells, they became more invasive," says Polyak.
Breast cancer starts in the lining of milk ducts when cells grow uncontrollably and may break out to invade breast tissue. Kornelia Polyak, MD, PhD, and colleagues show that noncancerous "stromal" cells outside the ducts can send signals that make the cancer more aggressive.
Illustration by John DiGianni
"The myoepithelial layer of the duct normally prevents DCIS from becoming an invasive condition," she adds. "If that layer disappears or weakens, the disease progresses. You can think of the myoepithelial layer as the inside of a tube: As long as it's intact, the DCIS cells can't escape. As the disease progresses, holes start to appear in the lining, allowing DCIS to spread."
Why does the myoepithelium take on the appearance of Swiss cheese? It appears that myoepithelial cells in DCIS have many abnormalities that prevent them from fully maturing, so they form a poor blockade against escaping tumor epithelial cells.
"We don't yet have a good understanding of the communications system between DCIS and the tissue of the milk ducts," Polyak says. "We'll be using xenograph models, in which human DCIS tissue is implanted in laboratory animals, to study the system in more detail. We hope to discover the signals that influence whether the disease remains isolated or becomes invasive."
