Mechanisms of lymphatic metastasis.

Malignant tumors release growth factors such as VEGF-C to induce lymphatic vessel expansion (lymphangiogenesis) in primary tumors and in draining sentinel LNs, thereby promoting LN metastasis. Surprising recent evidence suggests that lymphatic vessels do not merely represent passive channels for tumor spread, but that they may actively promote tumor cell recruitment to LNs, cancer stem cell survival, and immune modulation. New imaging approaches allow the sensitive visualization of the earliest LN metastases and the quantitative, noninvasive measurement of the function of tumor-draining lymphatic vessels, with potential applications in the development of biomarkers for prognosis and measurement of therapeutic response.