Stashed away in most of your tissues and organs lie small populations of adult stem cells. They help keep our bodies functioning properly by replenishing dying or damaged cells. Their ability to make more copies of themselves, as needed, ensures that there’s always an adequate supply set aside. But this very same self-renewing, life-sustaining property of adult stem cells is deadly in the hands of cancer stem cells. Also called tumor-initiating cells, cancer stem cells sustain tumor growth even after chemotherapy and are thought to be a primary cause of cancer relapse.
By studying adult and cancer stem cells side-by-side, Princeton researchers report this week in Nature Cell Biology that they’ve uncovered a common function in both cells types that not only helps explain an adult stem cell’s self-renewing ability but also points to new therapeutic approaches to targeting breast cancer stem cells.
Both adult and cancer stem cells continually resist signals from their environment that encourage them to specialize, or differentiate, into a particular cell type. Once specialized, the cells lose their ability to self-renew and will eventually die off. Now, if all the adult stem cells in an organ followed that instruction, they would eventually become depleted and the organ would lose the ability to repair itself. The same holds true for cancer stem cells which actually would be a good thing since it would lead to the tumor’s death.
The Princeton team first identified a molecule called mi199a that allows mammary (breast) stem cells to resist differentiation signals by directly blocking the production of a protein called LCOR. Artificially boosting the amount of mi199 led to a decrease in LCOR levels and an increase in stem cell function. But when LCOR levels were increased, mammary stem cell function was restricted.
The researchers then turned their attention to breast cancer stem cells and found the same mi199/LCOR function at work. In a similar fashion, boosting mi199 levels enhanced cancer stem cell function and increased tumor formation while increasing LCOR restricted the tumor-forming ability of the breast cancer stem cells.
These lab results also matched up with tissue samples taken from breast cancer patients. High mi199 levels in the samples correlated with low patient survival rates. But those with high levels of LCOR showed a better prognosis.
It turns out that cells in our immune system are responsible for boosting LCOR in mammary and breast cancer stem cells by releasing a protein called interferon alpha. So the presence of interferon alpha nudges mammary stem cells to mature into mammary gland cells and inhibits breast cancer stems from forming tumors. But in the presence of elevated mi199a levels, mammary and breast cancer stem cells are protected and maintain their numbers by deactivating the interferon alpha/LCOR signal.
If you’re still with me, these results point to mi199a as a promising target for restoring interferon-alpha’s cancer interfering properties. Team leader Dr. Yibin Kang highlighted this possibility in a Princeton University press release:
“Interferons have been widely used for the treatment of multiple cancer types. These treatments might become more effective if the interferon-resistant cancer stem cells can be rendered sensitive by targeting the miR-199a-LCOR pathway.”