The cellular mechanisms and regulation of metastasis formation

Data accumulating in biochemistry, molecular and cell biology, and experimental oncology indicate that metastasis, which is the formation of secondary tumor growth foci during cancer progression, is a highly determinate and regulated process. The process includes the emergence of a metastatic cell population possessing special properties to allow cell dissemination and seeding in distant organs and the formation of a specific microenvironment in target organs. Among other changes, metastatic cells display plasticity, being capable of switching their motility to the most efficient mode depending on the properties of surrounding tissues; start expressing specific surface receptors to ensure their migration to target organs; and acquire certain features of stem cells, being capable of surviving and reproducing in an alien microenvironment. A specific niche, known as the premetastatic niche, develops in the target organ in a strong coordination with the above changes to stimulate the initiation and growth of a prospective metastasis. The review considers the recent findings related to the mechanisms that regulate the emergence of the metastatic cell population, the formation of premetastatic niches, and the coordination of the two processes.