Invasion and Metastasis
Metastasis is responsible for more than 90% of cancer-related deaths. The invasion-metastasis cascade is a multi-step process, which involves the invasion of epithelial cells from the primary tumor into the adjacent stroma and through the extracellular matrix (ECM), intravasation of cancer cells into the bloodstream, their dissemination to distant sites, the formation of micrometastases, and finally the establishment of secondary tumors in distant organs.
Each of these complex events is driven by the deregulated molecular pathways that operate within tumor cells. Also, the cell-nonautonomous interactions between cancer cells and non-neoplastic stromal cells play a crucial role during the invasion-metastasis cascade. Altogether, this finally generates macroscopic, clinically detectable metastases with life-threatening abilities.
Breaking down the metastatic cascade into single steps and analyzing the different sub-processes, such as chemotaxis, (transendothelial) cell migration, cell behavior in the blood stream (cancer cells under shear stress), and rolling/adhesion, provides insights into the mechanisms of invasion and metastasis. These novel discoveries will bring progress to metastasis research, finally leading to novel basic research findings and their translation into the clinic.
Valastyan, S., & Weinberg, R. A. (2011). Tumor metastasis: molecular insights and evolving paradigms. Cell. 10.1016/J.CELL.2011.09.024