Abstract 1294: Inhibition of angiogenesis in lymph node metastasis

Abstract

Abstract Cancer invasion of the lymphatic system and spread to draining lymph nodes is a common occurrence and is often a first step of the metastatic pathway. Suppression of tumor angiogenesis in the lymph node should inhibit cancer growth and further spread from the lymph node. In the present study, we evaluated angiogenesis inhibitors in lymph node metastasis using GFP imaging. Transgenic nude mice expressing GFP under the control of the nestin promoter (ND-GFP mice) were used as hosts. Nascent blood vessels express GFP in these mice (Cancer Res. 65, 5352-5357, 2005). B16F10-RFP mouse melanoma cells were injected into the efferent lymph vessel of the inguinal lymph node of the transgenic ND-GFP nude mice to establish experimental metastasis in the axillary lymph node. The mice were given daily i.p. injections of doxorubicin or vehicle controls at days 0, 1, and 2 after implantation of tumor cells. The axillary lymph nodes of the mice were observed at day 8 after injection of tumor cells. Angiogenesis was quantified in the tumor-involved lymph node by measuring the total length of ND-GFP nascent blood vessels. The number of ND-GFP-expressing blood vessels in the tumor-involved lymph nodes was significantly less in the doxorubicin-treated animals than in vehicle control mice. Treatment with doxorubicin significantly decreased the volume of the metastatic axillary-node tumor as well as nascent blood vessel formation. These results show the utility of the dual-color ND-GFP-mouse and RFP-cancer-cell model to visualize and quantitate angiogenesis in tumor-involved lymph nodes and to screen for angiogenesis inhibitors at this site. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1294.