Abstract B109: Modulation of tumor-associated lymphatic function by the VEGF-C axis

Abstract

Abstract Lymph vasculature associated with solid tumors provides an exit route for disseminating metastatic cells. VEGF-C, a member of the vascular endothelial growth factor family, is upregulated in a range of metastatic tumor types. VEGF-C is known to mediate lymphatic development and is implicated in modulating lymph vessel function. These observations have lead to the hypothesis that VEGF-C expression in tumors may promote metastatic cell dissemination by augmenting lymph morphology or function. To explore this hypothesis we have developed longitudinal assays based on near-infrared fluorescence imaging technologies to study lymphatics associated with primary tumors. In preliminary experiments we observe a ∼ 50% increase in bulk transport through lymph beds draining VEGF-C(+) primary tumors. This increase in transport correlates with a ∼50% increase in contractile events along the draining vessels, suggesting that chronic production of VEGF-C promotes lymph transport in part by stimulating contractility. We are currently testing agents which block VEGF-C-mediated signaling pathways to determine if reduced signaling correlates with reduced transport and rates of metastatic events. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B109.