The mechanism by which VEGF-C increases the incidence of lymphatic metastasis is not known. In addition, the individual steps in lymphatic metastasis have not been imaged. Hoshida et al. developed novel technologies to image each step in the process of lymphatic metastasis including cell transport in lymphatic vessels and the arrival of cancer cells in lymph nodes. Using these methods, the authors discovered the mechanism of VEGF-C–induced lymphatic metastasis. VEGF-C increases lymphatic vessel diameter, lymph flow, and the number of tumor cells that enter the tumor-associated lymphatic vessels and travel to the draining lymph node. Pharmacological blockade of the VEGF-C signaling pathway reduced tumor cell delivery to lymph nodes, the initial step of metastasis. However, it could not prevent the growth of metastatic tumor cells already seeded in lymph nodes. For details, see the article by Hoshida et al. on page 8065 of this issue.

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