Origin and biology of cancer metastasis.

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.