The pre-metastatic niche: finding common ground.

It is rapidly becoming evident that the formation of tumor-promoting pre-metastatic niches in secondary organs adds a previously unrecognized degree of complexity to the challenge of curing metastatic disease. Primary tumor cells orchestrate pre-metastatic niche formation through secretion of a variety of cytokines and growth factors that promote mobilization and recruitment of bone marrow-derived cells to future metastatic sites. Hypoxia within the primary tumor, and secretion of specific microvesicles termed exosomes, are emerging as important processes and vehicles for tumor-derived factors to modulate pre-metastatic sites. It has also come to light that reduced immune surveillance is a novel mechanism through which primary tumors create favorable niches in secondary organs. This review provides an overview of our current understanding of underlying mechanisms of pre-metastatic niche formation and highlights the common links as well as discrepancies between independent studies. Furthermore, the possible clinical implications, links to metastatic persistence and dormancy, and novel approaches for treatment of metastatic disease through reversal of pre-metastatic niche formation are identified and explored.