Metastasis results from the acquisition of migratory and
invasive abilities as a result of not only accumulated mutations
and changes in gene expression, but also as a response
to stromal cell stimuli. One of the most dramatic changes
involves the loss of epithelial markers and the gain of
mesenchymal traits through a process termed epithelial to
mesenchymal transition (EMT). Cells that become metastatic
are able to locally invade the underlying mesenchyme,
intravasate into blood or lymph vessels, travel in circulation,
and then finally extravasate into a distal tissue for colonization
and the formation of a metastatic nodule resembling the
primary tumor.