THREE-DIMENSIONAL CHANGES IN LYMPHATIC ARCHITECTURE AROUND VX2 TONGUE CANCER - DYNAMIC CHANGES AFTER ADMINISTRATION OF ANTIANGIOGENlC AGENT

We examined the three-dimensional changes of the lymphatic architecture in the rabbit VX2 tongue cancer model after administration ofan antiangiogenic agent, TNP-470. TNP-470 at 30 mg/kg was administered via the auricular vein to the rabbit four times every other day from 3 days after transplantation of the tumor. The tongue and both sides ofdeep cervical lymph nodes of rabbit were observed at 10 days after transplantation. Lymph node metastasis was confirmed histopathologically. Morphological changes ofcollecting lymphatic vessels and lymphatic capillaries were observed, and the number and diameter of lymphatic vessels within 500 pm around the tumor were measured using the combined method with 5'-nucleotidase staining and three-dimensional reconstruction imaging. Tumor growth and lymph node metastasis were suppressed by administration of TNP470. In the TNP-treatment group, the mean number of lymphatic capillaries was significantly fewer than in the control group. The mean diameter ofcollecting lymphatic vessels was significantly smaller than in the control group. In conclusion, our results suggest that cancer cell invasion into the lymphatics is probably decreased by inhibiting not only the growth of tumor but also new formation of lymphatic capillaries around the tumor by administration of TNP-470. The dissemination of malignant cells from a primary tumor to local tissue or to distant organs via lymphatics or blood vessels is characteristic of cancer progression and is the major cause of mortality from malignant tumors (1). Cancer of the oral region tends to spread to regional lymph nodes relatively early (2,3). Therefore, it is important for the treatment of cancer to suppress not only the growth of the primary tumor but also the regional lymph node metastasis. Inhibition of angiogenesis has been developed recently as a new anticancer therapy (4) because solid tumors initiate an angiogenic process to support their growth (5). Interestingly, some reports have shown that antiangiogenic agents inhibit not only tumor growth but also lymph node metastasis (6-8). It is necessary to assess the effect of antiangiogenic agents on lymphatic vessels around tumors because metastasis to the cervical lymph nodes in oral cancer is established by cancer cells disseminating via lymphatic vessels. We have reported earlier that threedimensional changes occur in lymphatic architecture around the tumor during the development of cancer using the combination Permission granted for single print for individual use. Reproduction not permitted without permission of Journal LYMPHOLOGY .