Biophysical determinants of cancer organotropism

Metastasis remains the leading cause of cancer lethality. The 'seed/soil' hypothesis provides the framework to explain this cancer phenomenon where the concept of organotropism has been in part mechanistically explained by the properties of the tumor cells and their compatibility with the stromal environment of the distal site. The 'mechanical' hypothesis counters that non-random seeding is driven solely by the circulation patterns and vascular networks of organ systems. We incorporate concepts of mechanobiology and revisit the two hypotheses to provide additional insights into the mechanisms that regulate organ selection during metastatic outgrowth. We focus on the latter stages of the metastatic cascade and examine the role of the endothelium in regulating organ selectivity.