Fig. 2.

Mechanism of lymphatic metastasis and its inhibition. a. Tumor cells invade into the surrounding tissues and co-opt pre-existing lymphatic vessels. Two important events are required for lymphatic metastasis, which are lymphatic vessel sprouting and dilation of collecting vessel diameter. These events facilitates tumor invasion and spread via lymphatic vessels. Shown in panel a is a representative lymph node with metastatic tumor cells overexpressing luciferase, performed using the in vivo bioluminescence imaging system (Caliper Xenogen). b. Inhibition of lymphatic metastasis can be achieved by employing reagents such as soluble receptors against VEGFR-3 and TIE-2 signaling pathways. In the case of VEGFR-3 blockade, tumor lymphangiogenesis, including lymphatic vessel sprouting and vessel dilation, is inhibited. This results in the efficient suppression of tumor cell entry into lymphatic vessels. Interestingly, suppression of TIE-2-mediated pathway could also efficiently block lymphatic metastasis, but do not have appreciable effects on tumor-associated lymphangiogenesis. The mechanism of TIE-2-mediated signaling in tumor metastasis is still to be investigated. Tu, tumor; Ne, necrosis