Origin and biology of cancer metastasis

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Abstract
Metastasis, the spread of cells from a primary neoplasm to distant sites where they grow, contributes to the death of most cancer patients. The process of metastasis is not random. Rather, the process consists of a series of linked, sequential steps that must be completed by tumor cells if a metastasis is to develop. Thus, metastatic cells must succeed in invasion and embolization, survive in the circulation, arrest in a distant capillary bed, and extravasate into and multiply in organ parenchyma. Although some of the steps in this process contain stochastic elements, as a whole metastasis favors the survival and growth of a few subpopulations of cells that preexist within the parent neoplasm. Moreover, metastases can have a clonal origin, and different metastases can originate from the proliferation of single cells. The outcome of metastasis depends on the interaction of metastatic cells with different organ environments. Organ‐specific metastases have been demonstrated in a variety of experimental tumor systems, and even within one organ, site‐specific tumor growth can be found. The conclusion that metastasis is a highly selective process that is influenced by both the intrinsic properties of tumor cells and by host factors is optimistic. A selective process is regulated and therefore can be studied and then manipulated.