Identification of Metastatic Tumor Stem Cell

More than 90% of deaths caused by breast cancer are attributed to metastatic disease. However, the exact molecular mechanism of tumor metastasis is still poorly understood. It has been well recognized that only a fraction of cells in the primary tumor eventually metastasizes to the distant organs; however, the origin and nature of these cells are still unclear. The purpose of this project is to test our novel hypothesis that metastatic cells originate from a distinct tumor cell population which has both stem-like properties and an invasive ability. We have successfully isolated the cell population (CD24-/ CD44+/ ESA+) that has tumor initiating ability as well as metastatic capability. The expression profile analysis revealed that the HAS2 gene plays a critical role in the process of bone metastasis of CSCs, which was also strongly supported by our results of in vivo experiment. Interestingly, small molecule HAS2 inhibitor, 4MU, was shown to significantly suppress the CSC-induced bone metastasis. Therefore, our results open a possibility of using 4MU for the treatment of metastatic bone disease.
The original document contains color images.