Regulation of tumor cell growth at organ-specific metastases.

The hallmark of malignant neoplasms is their ability to spread beyond the site of origin and produce metastases in distant organs. This nonrandom process depends on the interaction of specific tumor cells with a compatible milieu provided by a particular organ microenvironment; the molecular basis of which is under intense investigation. Recent analysis of human colon carcinoma (HCC) cells obtained from surgical specimens and implanted into athymic nude mice suggested that whereas nonmetastatic and highly metastatic cells can grow at local sites, growth per se in the secondary organ-specific site was associated only with high-metastatic HCC cells. These cells also respond in a specific manner to physiological mitogenic signals produced by damaged normal tissues. This article addresses the biological and molecular evidence supporting the hypothesis that organ-derived, perhaps, organ-specific, paracrine growth factors stimulate the growth of receptive malignant cells that possess the appropriate receptors.