Development of a computer-assisted high-throughput screening platform for anti-angiogenic testing

Angiogenesis is widely accepted to play a central role in tumor growth and spreading. Therefore, anti-angiogenic agents appear as promising tools in cancer therapy, and great efforts have been devoted to their identification in recent years. Despite fast progress in this area, a quantitative and objective system for rapid anti-angiogenic testing is not currently available. In this work, we describe a new platform for the large-scale screening of agents with potential anti-angiogenic activity. This involved the miniaturization of an in vitro two-dimensional assay model of vascular morphogenesis to run in a high-density format (384- or 1536-well microplates) and the development of a specific digital image-analysis system for the automated and quantitative evaluation of biological activity. To test the efficacy and reproducibility of the platform, we used a wide variety of well-characterized angiogenesis inhibitors, including antibodies against components of the extracellular matrix, peptides, and chemicals. The system proved to be a reproducible, polyvalent, and powerful tool for massive screening of agents with potential application in cancer therapy. Ongoing developmental work, directed toward optimizing this system for use with a fully automated high-throughput screening platform, should accelerate research into the mechanisms of tumor angiogenesis and the development of drugs that target the essential tumor vasculature.