Breast cancer has proved especially difficult to find and fight due to the cancer cells' ability to blend in with healthy ones. Careful examination of the chemical makeup and shape of normal and diseased cells, however, promises to help doctors draw cancer out of the shadows.
Researchers at University of Michigan's Comprehensive Cancer Center in Ann Arbor report in Cell Stem Cell that they found a marker that can be used to identify cancer stem cells in breast tumors. Even though they account for only 5 percent of cells in tumors, stem cells (defined by their ability to generate identical cells and to morph into other cell types) are believed to play a key role in the spread of cancer.
The Michigan study, which began in late 2004, indicates cells from normal and cancerous breast tissue that contain high levels of the enzyme group aldehyde dehydrogenase (ALDH) acted like stem cells. Of the 577 human breast cancer tissue samples studied, those with tumors that tested positive for ALDH1—a specific form of the enzyme—were less likely to survive and were 1.76 times more likely to develop metastases than patients with ALDH1-negative tumors. ALDH1 was found in 19 percent to 30 percent of the study samples.
The presence of ALDH1 in both normal and malignant stem cells supports the theory that they are the primary target of transformation to malignancy, says study senior author Gabriela Dontu, an assistant professor of internal medicine. "We believe it is only a very small population of cells that really are capable of unlimited growth and therefore drive cancer recurrence and metastasis," she says. "The fact that normal and cancer stem cells share a common feature gives more support that cancers arise from normal stem cells."
The clinical implications of this stem cell model of carcinogenesis "changes the way we approach early diagnostic prognosis and, very importantly, how we develop therapy," Dontu adds. As the research progresses, she and her colleagues plan to develop therapeutic strategies that might eliminate cancer stem cells in breast tumors and cancers from other tissues. The researchers acknowledge, however, that more work is needed before these findings can be applied in clinical tests or treatments.
In a related study, a group of University of California, Los Angeles, researchers are hunting specifically for the cancer cells in body cavity fluids. The team reports in the online edition of Nature Nanotechnology that conventional diagnostic methods—such as using cell markers—detect about 70 percent of cases in which cancer cells are present in the fluid, but miss the rest.
The U.C. Los Angeles researchers, using an optical microscope, found that normal and cancer cells extracted from chest cavity fluid of patients with lung, breast and pancreatic cancers looked very similar. But when they attached an atomic force microscope (AFM) to the ordinary optical scope, they were able to use its minute, sharp tip to "feel" the cells, by pushing against a cell's surface to determine its degree of softness, says study co-author Jianyu Rao, a researcher at U.C.L.A.'s Jonsson Comprehensive Cancer Center and an associate professor of pathology and laboratory medicine.
An AFM is not actually a microscope but rather a device with an extremely small silicon probe that can be attached to an optical microscope for imaging, measuring and manipulating matter at the nanoscale. "It's like a finger that feels the softness of a cell," says James Gimzewski, a U.C.L.A. professor of chemistry and biochemistry and a member of the school's California NanoSystems Institute. The probe's tip is typically no larger than 20 nanometers in diameter.