Predicting breast cancer metastasis; formation of the pre-metastatic niche.
Summary
The leading cause of death in breast cancer patients is tumor metastasis. This process includes several steps that all need to be completed successfully to develop distant metastatic disease. Tumor cells disseminate from the primary tumor and cross multiple barriers like the basement membrane and extracellular matrix. Subsequently, tumor cells enter the circulation by a process called intravasation, and they are transported throughout the body. At specific sites, tumor cells adhere to the blood vessel walls, breach the vascular endothelium (extravasation) and colonize target organs. Breast cancer shows striking tissue tropism for the formation of metastases in lung, bone, brain and liver. The molecular mechanisms underlying this specificity are not yet known, but most likely it is caused by an interplay between tumor cells and the microenvironment at target organs. Studies have shown that, before arrival of tumor cells, the microenvironment in target organs is modulated to form a permissive ‘pre-metastatic niche’. Unraveling the mechanisms underlying the formation of this ‘pre-metastatic niche’ might contribute to our ability to predict breast cancer metastasis and the development of specific anti-cancer drugs and therapies.