Lymphatic dissemination of tumour cells and the formation of micrometastases

Most human cancers show evidence of metastatic spread to regional lymph nodes, and the extent of lymph-node involvement is directly related to clinical outcome. Increased expression of vascular endothelial growth factor C in primary tumours is associated with increased dissemination of tumour cells to regional lymph nodes in various human carcinomas. Arguments favouring the activation of preexisting lymphatic endothelium and the de novo formation of lymphatic capillaries (lymphangiogenesis) are discussed. We highlight recent advances in the molecular detection and characterisation of lymph-node micrometastases, as well as potential microenvironmental factors, such as chemokines, which may influence the migration and growth of metastatic tumour cells. Finally, we examine the clinical significance of lymphatic-mediated tumour-cell dissemination and the formation of lymph-node micrometastases.