The role played by the microenvironment in site-specific metastasis

Cancer cells that disseminate to metastatic sites may progress to frank metastasis or persist as dormant micrometastasis. Significant progress has been made in defining the genetic and phenotypic cancer-cell-autonomous determinants of metastasis and in the understanding of the cross-talk between metastasizing tumor cells and the metastatic microenvironment.However several questions remain open, in particular the identity of microenvironmental factors that keep micrometastatic cells in a state of dormancy and those that promote survival, proliferation and progression of such cells. Significantly more information is available on the latter factors than on microenvironmental cells and molecules that restrain micrometastasis. This mini-review summarizes findings suggesting that:. •The interactions between the metastatic microenvironment and cancer cells metastasizing to this microenvironment are unique to each metastatic microenvironment.•cells or molecules in the metastatic microenvironment could act as "double agents" exerting pro- or anti-malignant functions.•In the early phases of tumor progression, the interactions between cancer cells and the metastatic microenvironment are inhibitory whereas in later stages such interactions promote progression towards metastasis.In view of the above, it is not unlikely that metastases residing in different microenvironments may require "individualized" treatment modalities.