BCM researchers advance breast cancer stem cell research
Baylor College of Medicine researchers presented new data regarding breast cancer stem cells, the unique subset of breast cancer cells that are capable of initiating tumor growth and are relatively resistant to chemo and radiotherapies, today at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium.
The conference is co-sponsored by BCM, the American Association of Cancer Research and the Cancer Therapy and Research Center at the University of Texas Health Science Center in San Antonio.
"This is a major clinical problem that basic science breast cancer researchers are working to solve – gaining a better understanding of the molecular characteristics of these cells will help," said Dr. Michael Lewis, an associate professor of molecular and cellular biology and radiology, and a member of the Lester and Sue Smith Breast Center at BCM. "These cells appear to be responsible for recurrence of the disease and for spread to other organs in the body."
Researchers in Lewis' lab presented new information in poster presentation sessions at the breast cancer meeting.
Identifying the cellular signaling pathways responsible for breast cancer stem cell maintenance and self-renewal represents a critical hurdle for developing effective therapies, wrote the BCM researchers, led by Wei Wei, a graduate student in Lewis' lab, in the abstract of their study.
In their study, the team focused on the Stat3 pathway, a critical regulator of the function of stem cells.
Using a new fluorescent reporter, they verified recent studies that showed Stat3 signaling is active in a small subpopulation of cells in both patient xenografts (human tumor tissue grown in mice) and breast cancer cell lines.
Preliminary data suggests that high Stat3 signaling correlates with stem cell function.
Potential therapeutic targets
In a separate study Dr. Xiaomei Zhang, a research associate in the Lewis lab, and her colleagues, evaluated two different inhibitors of the "Hedgehog" signal transduction network as potential therapeutic agents.
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. Several signal transduction networks, including Hedgehog, have been implicated in normal and cancer stem cell self-renewal, the researchers wrote.
Zhang and her team focused on the Hedgehog signaling network, and compared two different antagonists, one targeting the Smoothened protein and one targeting the GLI1 and GLI2 proteins.
Though inhibitors both showed little effect as single agents, when used in combination with chemotherapy tumor shrinkage was augmented.
The data suggest that combination therapy alters the functional state of stem cells as a consequence of interactions between stem cells and other cells within the tumor, rather than targeting the tumor initiating cells directly