Abstract 5233: Abnormal lymphatic drainage and function from vascular endothelial growth factor (VEGF)-C overexpressing B16F10 melanoma

Abstract

Abstract The lymphatic system provides a major transport route for initial cancer cell dissemination for many cancers. Tumor lymphangiogenesis (i.e., the new formation of tumor-associated lymphatic vessels) is associated with metastatic potential and is an emerging therapeutic target to arrest metastasis. Recent studies show that the major lymphangiogenic growth factor, vascular endothelial growth factor (VEGF)-C induces tumor lymphangiogenesis and enhances tumor spread to the regional lymph nodes (LNs) and distant sites in mouse models of breast cancer and melanoma. Yet despite the important role of lymphatics as a critical pathway for cancer metastasis, relatively little is known about lymphatic function during tumor progression and metastasis, due mainly to the lack of lymphatic imaging approaches. Recently, we have developed in vivo dynamic near-infrared (NIR) fluorescence imaging methods for quantifying propulsive lymph flow. Herein, we employed a dynamic, functional lymphatic imaging technique and longitudinally imaged spatial and temporal changes in lymphatic function and architecture in mice bearing vascular endothelial growth factor (VEGF)-C overexpressing B16F10 (VEGF-C-B16F10) or mock-transduced B16F10 (mock-B16F10) melanoma tumors. C57BL6 mice were injected with 10ul of indocyanine green (ICG) or FITC-Dextran in the base of the tail and were dynamically imaged for baseline information before implantation of VEGF-C-B16F10 or mock-B16F10 in the hindlimb every three to four days for up to 27 days after inoculation. Our dynamic NIR fluorescence imaging data show that ICG-laden lymph accumulates into a VEGF-C-B16F10 tumor at 3 days post implantation as confirmed with FITC-Dextran leakage from lymphatic vessels; thereafter lymphatic leakage is visualized only in peritumoral lymphatic vessels. Our longitudinal imaging data also show dilated and tortuous lymphatic vessels and reduced or loss of propulsive lymphatic flow in the process of VEGF-C-B16F10 growth. However, mock-B16F10 tumors do not show lymphatic vessel leakage during tumor progression. NIR fluorescence imaging technology can be used to non-invasively and quantitatively detect functional lymphatic changes associated with cancer, which may enable accurate nodal staging of cancer patients and provide new approaches to diagnose and treat cancer metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5233. doi:10.1158/1538-7445.AM2011-5233