Metastasis is a highly selective nonrandom process favoring the survival of minor subpopulations of metatastatic cells that preexist within the primary tumor. The cellular and molecular mechanisms that regulate the metastasis of tumor cells to specific organs are diverse and both tumor and organ-specific (1). Many examples exist in which malignant tumors metastasize to specific organs. As Paget proposed in 1889 (2), and as our recent biological and molecular evidence demonstrates, the organ microenvironment influences the invasion, survival, growth, and apoptosis of particular tumor cells. This hypothesis explains metastatic colonization patterns that cannot be due to solely mechanical lodgement/anatomical considerations (1). Successful metastasis therefore involves the interaction of tumor cells with a compatible milieu provided by a particular organ environment.

Recent experimental evidence suggests that paracrine stimulation of tumor cells by organ-derived growth factors and cytokines is one mechanism which determines the target organ preference of disseminated cancer cells.