Environmental control of invasiveness and metastatic dissemination of tumor cells: the role of tumor cell-host cell interactions

Recent advances in tumor biology led to the realization that, in order to understand the mechanisms involved in proliferation and invasion of tumor cells, an analysis of the complex interactions that tumor cells establish with host cells of tumor microenvironment is required. The bidirectional interactions between tumor cells and components of tumor microenvironment, in particular endothelial cells, cells of monocyte/macrophage lineage and fibroblasts/myofibroblasts, play a critical role in most of the events that characterize tumor progression and metastasis. Interactions between these "reactive" normal cells and the genetically altered tumor cells, by either cell-to-cell contacts or soluble mediators, control the most aspects of tumor formation and progression. This review addresses some of the experimental evidences documenting that tumor cells may influence host cells of their own microenvironment by triggering changes that facilitate their local as well as distant dissemination. Therefore, it focuses on macrophages and fibroblasts that, upon stimulation by tumor cells, change their state towards a tumor-promoting-like phenotype.