By manipulating highly specific gene-regulating molecules called microRNAs, scientists at Cold Spring Harbor Laboratory (CSHL) report that they have succeeded in singling out and repressing stem-like cells in mouse breast tissue - cells that are widely thought to give rise to cancer.
“If certain forms of breast cancer do indeed have their origin in wayward stem cells, as we believe to be the case, then it is critical to find ways to selectively attack that tumor-initiating population,” said Gregory Hannon, Ph.D., CSHL professor and Howard Hughes Medical Institute Investigator. Hannon also is head of a lab focusing on small-RNA research at CSHL and corresponding author of a paper reporting the new research, published in the latest issue of Genes and Development.
“We have shown that a microRNA called let-7, whose expression has previously been associated with tumor suppression, can be delivered to a sample of breast-tissue cells, where it can help us to distinguish stem-like tumor-initiating cells from other, more fully developed cells in the sample. Even more exciting, we found that by expressing let-7 in the sample, we were able to attack and essentially eliminate, very specifically, just that subpopulation of potentially dangerous progenitor cells.”
The study was done in collaboration with Senthil Muthuswamy Ph.D., an expert in breast cancer research who heads a CSHL lab focusing on understanding the changes in the biology of breast epithelial cells during the initiation and progression of cancer. Dr. Muthuswamy emphasized that a key ingredient that made this study successful is the use of a mouse breast-derived model cell system called COMMA-1D that not only includes differentiated cells but also stem-like progenitors, in varying stages of maturity, or differentiation.
Unexpected Impact of Conventional Chemotherapy
No therapies currently exist that target stem-like tumor-initiating cells, whose existence in diverse tissues including breast, lung, brain and colon, as well as in the blood, has been demonstrated in a line of research stretching back to 2001. In that year, John E. Dick of the University of Toronto identified cancer stem cells in the blood of leukemia patients.