MOLECULAR MECHANISMS FOR ORGAN-SPECIFIC COLON-CARCINOMA METASTASIS

The mechanistic basis of a metastatic cell's ability to proliferate in the parenchyma of certain organs and develop organ-specific metastases remains largely unknown. Signals from paracrine and/or autocrine pathways may regulate tumour cell proliferation, with the eventual outcome dependent on the net balance of stimulatory and inhibitory factors. Recent data demonstrate that organ microenvironments can modulate gene expression of tumour cells, including regulation of growth at the organ-specific metastatic site. Analyses of highly metastatic human colon carcinoma (hCC) cells selected in nude mice as well as in situ mRNA hybridisation analyses of archival colon carcinoma specimens correlated high levels of epidermal growth factor receptor with the malignant hCC cell's ability to grow in the liver parenchyma. These same metastatic cells can also respond to specific mitogens produced by tissue undergoing repair, demonstrating that physiological signals can be utilised by neoplastic cells. This article will address experimental evidence supporting the premise that organ-derived, paracrine growth factors regulate the growth of malignant cells that express the appropriate receptors.