A dual-color fluorescence imaging-based system for the dissection of antiangiogenic and chemotherapeutic activity of molecules SHILADITYA SENGUPTA, TANYEL KIZILTEPE and RAM SASISEKHARAN 1 Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA 1 Correspondence: 16-560, Biological Engineering Division, M.I.T., 77 Massachusetts Ave, Cambridge, MA 02139, USA. E-mail: rams@MIT.edu <h3>SPECIFIC AIMS</h3> Our purpose was to develop a 3-dimensional dual fluorescence imaging-based in vitro culture system that allows the dissection of angiotherapeutics from chemotherapeutics, integrating the extracellular matrix as a key component modulating the outcome. <h3>PRINCIPAL FINDINGS</h3> <h3>1. VEGF and HGF induce tumor angiogenesis in vitro, which can be pharmacologically dissected at the receptor level using PTK787</h3> Endothelial cells formed a limited number of tubular networks within 24 h of plating on matrigel (1:3 dilution). However, the addition of tumor cells to establish the coculture accelerated the tubulogenic process. The GFP+ tumor cells were visualized to concentrate into clusters surrounded and integrating with the vascular network. Addition of both VEGF and HGF/SF resulted in a significant increase in the vascular network. To validate the sensitivity of the system to elucidate the modulation of specific pathways, we used a VEGF receptor antagonist, PTK787. As expected, VEGF-induced angiogenesis was blocked by
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A dual-color fluorescence imaging-based system for the dissection of antiangiogenic and chemotherapeutic activity of molecules
SENGUPTA, SHILADITYA; KIZILTEPE, TANYEL; SASISEKHARAN, RAM
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, Volume 18 (13): 1565
Fed of American Socs for Experimental Biology – Oct 1, 2004
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