Victor P. Terranova

Tumor cell metastasis

Local tissue invasion and the formation of metastatic lesions are characteristic properties of many malignant tumors. The formation of metastases is a complex process involving the passage of tumor cells from the site of the primary bulk tumor through successive connective tissue barriers, ultimately resulting in the growth of secondary tumor cell colonies in distinct target organ locations. At many stages in the metastatic process, tumor cells interact with multiple components of the extracellular matrix. Recently, the importance of basement membrane as a barrier to invasive cells has been recognized. In the course of the transition from in situ to invasive carcinoma, normal or dysplastic epithelial cells residing on a basement membrane are replaced by neoplastic cells which subsequently invade the basement membrane and enter the underlying stroma. Once in the stroma, tumor cells can then penetrate the walls of blood vessels or the lymphatic system and enter into the circulation. Circulating tumor cells next arrest in the lumina of small vessels, invade the vessel wall, and leave the circulation. These cells are now directly exposed to the extracellular matrix of a target organ where they may grow to form secondary tumors. Throughout the metastatic process tumor cells are thus in contact with, and are potentially responsive to, various components of the extracellular matrix. This review provides a survey of the recent advances in our understanding of the interactions of metastatic tumor cells with the extracellular matrix. Specifically, the role of basement membrane as a barrier to metastatic tumor cells is examined.