A new player in tumor metastasis

Primary tumors metastasize to distant locations through a process called endothelial to mesenchymal transition (EMT). Tumor cells have to move from the primary location, enter the bloodstream, travel to the distant site, enter that tissue and begin to grow in the new environment. In order to accomplish this, tumor cells alter the genes that are expressed. Breast tumor cells, for example, are epithelial cells that have begun to grow uncontrollably. As these cells emerge from the breast and enter into the bloodstream, many genes that define the tumor as a epithelial cell are switched off and genes that allow for movement (mesechymal genes) are turned on. Therefore, due to changes in the gene expression, primary breast tumors emerge from the breast, enter the bloodstream, and migrate to the lung where metastatic disease occurs. Scientists can detect the profiles of genes that change when tumors become metastatic, but how this switch occurs still remains unclear.

In a recent article in Oncogene (2011, 30:3440-3453) Dr. Xiang and colleagues at the University of Louisville, the University of Alabama, and the Louisville Veterans Administration Medical Center have provided new insight into how these genes are activated or inhibited. Their study shows that a gene regulator, called miR-155, acts as a switch that prevents breast tumor cells from migrating from the breast into the blood. Surprisingly, they also found that miR-155 can promote the formation of lung metastases if the tumor cells have already entered the bloodstream. While miR-155 appears to decrease the expression of genes involved in EMT and movement from the primary site, if tumor cells do manage to migrate, miR-155 can help promote their migration and growth in the lung. This is a bit of a double edged sword. These data do suggest that activation of miR-155 when breast tumor cells are confined only within the breast could be effective to prevent metastasis, however if the breast cells have already left the breast location, then activation of miR-155 will promote metastasis.