After they confirmed the metastasis-inducing properties of the miRNAs, the research team began searching for their target genes in MCF-7 cells. Several experiments limited the search to a gene called CD44, which contains genetic instructions for a common cell surface receptor molecule. Found in most cell types, CD44 affects cell-cell interactions and interactions between cells and their microenvironments. It also has been shown to inhibit tumor metastasis.
When CD44 was downregulated, non-metastatic MCF-7 cells became metastatic. When the scientists injected MCF-7 cells without CD44 into immunodeficient mice, the mice developed bone and lung tumors, while mice receiving MCF-7 cells with CD44 did not.
We found that miR-373 and miR-520c interfered with the expression of CD44 in MCF-7 cells, Huang says. We think there are additional targets involved, but our results suggest that these miRNAs promote cell metastasis at least in part by limiting the expression of CD44.
In the final stages of the study, Huang and his colleagues analyzed 11 pairs of primary and metastatic breast cancer tissue samples from cancer patients. The scientists found that metastatic tumors removed from lymph nodes contained more miR-373 than the primary breast tumor from the same patient.
An additional study of 72 human primary breast tumors found higher mean expression of miR-373, and lower mean expression of CD44, in primary tumors from patients whose cancer had spread to their lymph nodes compared to patients whose tumors had not spread.
According to Huang, these results suggest miR-373 has the potential to become an important early biomarker for metastatic breast cancer. As far as we know, miR-373 is not expressed in normal tissue, Huang says. So if we detect miR-373 in lymph nodes when a patients breast tumor is removed, it would i
|Contact: Abbey J. Porter|
The Wistar Institute