Metastasis begins with the invasion of tumor cells into the stroma and migration toward the blood stream. Human pathology studies suggest that tumor cells invade collectively as strands, cords and clusters of cells into the stroma, which is dramatically reorganized during cancer progression. Cancer cells in intravital mouse models and in vitro display many 'modes' of migration, from single isolated cells with round or elongated phenotypes to loosely-/non-adherent 'streams' of cells or collective migration of cell strands and sheets. The tumor microenvironment, and in particular stroma organization, influences the mode and dynamics of invasion. Future studies will clarify how the combination of stromal network structure, tumor cell signaling and extracellular signaling cues influence cancer cell migration and metastasis.
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