Lymphatic invasion and metastasis

The 2 phenomena are reviewed (121 references). The invasion of lymphatics must depend on the same factors as are involved in neoplastic invasion in general: cell motility, lack of adhesiveness, release of lytic enzymes, increase in cell population and tissue pressure and active migration of cells. Lymphatic metastasis consists of: entrance in the peripheral lymphatics; with subsequent embolism, lodgement and growth in the draining lymph node. Study of lymphatic metastasis in animals requires precise and defined models. In the only model studied it seems that initial penetration occurs by reverse diapedesis of tumor cells through open endothelial junctions. Lymphocytes and macrophages migrate into lymphatic vessels in a similar way. It is likely but not certain that in some way the cells induce opening of lymphatic endothelial junctions. Whether this process is specific or non-specific and whether it involves release of chemical mediators is uncertain. There is some evidence that in one model there is induction selection of one tumor subtype for successful metastasis, though it is far from certain that this is universally true. The cellular reactions in the draining lymph node include sinus macrophage proliferation, proliferation of cells in germinal centers, and migration of cells from post-capillary-venules. A definable burden of tumor cells in the node is necessary for successful metastasis; this burden is much smaller than that necessary for growth in the primary inoculation site, indicating a degree of immunologic privilege within the node. A lymphoreticular and therefore presumably immunologic reaction in either primary injection site or node may result in tumor rejection. The influence of the lymph node on the process of metastasis is dubious. Lymph nodes are no effective barriers against cancer cells. There is much controversy both on the effect of the lymphoreticular response (enhancing or retarding growth) as well as on the effect of regional lymph node removal. While the 2 major methods of dissemination of cancer (by blood and by lymph) are closely related, there may be differences in sensitivity to chemotherapy; in one model lymph node metastases have been shown to be more sensitive to chemotherapy. There is great need for experiments on lymphatic metastasis to provide guidelines for new approaches to the treatment, and even prevention of metastasis in human cancer.