Figure 1. Crosstalk between tumor hypoxia and the lymphatic and blood vasculatures. Hypoxic tumor cells (blue) near pre-existing blood and lymphatic vessels secrete angiogenic and lymphangiogenic growth factors such as VEGF-A, -C, and –D. Blood vessels bring oxygen and nutriments to tumor cells, whereas lymphatics drain debris and provide new routes for tumor metastasis. Lymphatic metastatic tumor cells maintain lymphangiogenic growth factors synthesis in this poorly oxygenated environment to promote lymph node lymphangiogenesis and establish the “metastatic niche.”