Researchers at the Cold Spring Harbor Laboratory (CSHL) have identified the stem-like cells in mouse breast tissue, which are thought to give rise to cancer.
The mouse-based study, conducted by 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 and Gregory Hannon, Ph.D., CSHL professor and Howard Hughes Medical Institute Investigator, manipulated highly specific gene-regulating molecules called microRNAs in singling out and repressing the stem-like cells.
"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 tumour-initiating population," Hannon said.
"We have shown that a microRNA called let-7, whose expression has previously been associated with tumour suppression, can be delivered to a sample of breast-tissue cells, where it can help us to distinguish stem-like tumour-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," he added.
Muthuswamy emphasized that a key ingredient that made the finding a possibility was 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.
The research not only suggests one possible way of accomplishing the therapeutic goal, the Hannon lab researchers are initiating a demonstration study in mice but it also demonstrated that one component of a chemotherapy cocktail currently used as first-line therapy against certain kinds of breast cancer has the potential to actually enrich the subpopulation of stem-like cells that serve as cancer progenitors.
"We found that administration of cyclophosphamide in our mouse cell sample had the effect of enriching for these cells, which suggests that we need to look carefully at these therapies in model systems to see if the effects we see in cell culture are mirrored in real tumours - and then, to gauge what effect that has on metastasis and relapse following therapy," Hannon said.
The study is published in Genes and Development.