In a study published online in advance of print in Stem Cells, Tufts researchers report that the STAT3 gene regulates cancer stem cells in brain cancer. Cancer stem cells have many characteristics of stem cells and are thought to be the cells that drive tumor formation. The researchers report that STAT3 could become a target for cancer therapy, specifically in Glioblastoma multiforme (GBM), a type of malignant and aggressive brain tumor.
Patients with Glioblastoma multiforme typically survive 12 to 14 months with treatment. Treatment options include radiation, chemotherapy, and surgery.
"When STAT3 is inhibited, cancer stem cells in glioblastomas lose their stem-cell characteristics permanently, suggesting that STAT3 regulates growth and self-renewal of stem cells within glioblastomas. Strikingly, a single, acute treatment with STAT3 inhibitors was effective, implying that a STAT3 inhibitor could stop tumor formation," said senior author Brent Cochran, PhD, a professor at Tufts University School of Medicine and a member of the cellular & molecular physiology program faculty at the Sackler School of Biomedical Sciences at Tufts.
"STAT3 has been shown to be activated in a number of human tumors. This study is one of the first to show, however, that STAT3 regulates cancer stem cells. It is one of the few genes linked to the propagation of cancer stem cells, and it appears to regulate processes involved in the six hallmarks of cancer: growth, metastasis, angiogenesis, evasion of apoptosis, tissue invasion, and cell immortalization," he continued.
The researchers used cancer stem cells isolated from surgically removed samples of glioblastoma tumors. Cell cultures were treated with two chemically distinct small-molecule inhibitors (STA-21 and S3I-201) of STAT3. After several days of treatment, cell growth in the STAT3-inhibited cultures was minimal compared to growth in the control cultures. Moreover, in the STAT-inhibited cultures, proteins that help maintain stem-cell characteristics were apparently turned off. This finding leads the researchers to believe that STAT3 has a distinct role to play in cancer stem cells, which may make it an especially good target for cancer therapy.