Paracrine/autocrine growth mechanisms in tumor metastasis.

The successful growth of metastatic tumor cells is due to their responses to local paracrine growth factors and inhibitors and their production and responses to autocrine growth factors. At early stages of metastatic progression, there is a tendency for many common malignancies to metastasize and grow preferentially at particular sites, suggesting that paracrine growth mechanisms may dominate the growth signals affecting metastatic cells. At later stages of metastatic progression, where widespread dissemination to various tissues and organs occurs, autocrine growth mechanisms may dominate the growth signals affecting metastatic cells. The progression of malignant cells to completely autonomous (acrine) states can ultimately occur, and at this stage of metastatic progression cell growth can be completely independent of growth factors or inhibitors. Various strategies have been developed to treat cancer that are based on the responses of malignant cells to growth factor or inhibitor analogs, anti-receptor antibodies, or antibody- or growth factor-toxin conjugates. Since the responses and expression of growth factor receptors can change during malignant progression, the development of cancer treatments using analogs of specific growth inhibitors or antagonists of growth factors, such as monoclonal antibodies or other agents, to block growth signaling mechanisms may only be useful at the early stages of malignant cancer progression before widespread metastasis of acrine cells occurs.