An independent publication cites using ATCC Angio-Ready angiogenesis kit to identify drugs that inhibit HIF-1 signaling

Green vessels on purple backgroundAngiogenesis, or the formation of blood vessels, is an essential process for an animal’s growth and homeostasis. This process is heavily regulated to ensure that it results in consistent blood flow to the tissues and organs. It is also misregulated in many disease states. For example, in cancer angiogenesis is upregulated by tumor cells to increase their growth and to provide a mechanism for metastasis.

New tools are needed to study this process, such as ATCC’s new Angio-Ready™ Angiogenesis Assay System. Angio-Ready consists of a mixture of hTERT-immortalized aortic endothelial cells that express GFP, hTERT-immortalized mesenchymal stem cells, and a specialized growth medium. In the high-throughput, scalable assay the cells form tubules reminiscent of in vivo angiogenesis which can be captured by live-imaging and then quantified using imageJ-type software2.

A group in the National Center for Advancing Translational Sciences at the NIH led by Dr. Menghang Xia has recently sought to identify drugs that are either on the market or under investigation to determine if any inhibit hypoxia-inducible factor 1 (HIF-1) signaling. This signaling pathway is responsible for the secretion of many pro-angiogenic factors resulting in the sprouting and formation of new blood vessels.

The first step in the process for Dr. Xia and colleagues was to screen a HIF-1alpha reporter cell line for growth inhibition using over 2000 drugs and 960 druggable targets on a high throughput screening platform. Candidate drugs were then further analyzed for their anti-growth effects. ATCC’s Angio-Ready came in to play when 10 likely compounds, shown by the authors to affect HIF-1 signaling, were tested for their ability to inhibit vascular endothelial growth factor (VEGF)-stimulated angiogenesis1.

The authors observed that the inhibitors, such as mycophenolate mofetil, PI-103, trametinib, and niclosamide, could potently block angiogenic tubule formation in our co-culture system. After 3 days of exposure to these compounds angiogenesis was reduced dose dependently in a manner similar to what was seen in the positive control treatment. The authors concluded that further work will be needed before these drugs can be indicated for use as anti-angiogenics1. For ATCC, this study represents a successful beta test for Angio-Ready.

Xia and colleagues observations echo those seen at ATCC’s Research and Development laboratory. We recently posted on our website an application note showing that VEGF concentration-dependently stimulated vascular tubule formation. Interestingly, the formation of these tubules was inhibited by treatment with the drugs suramin, sunitinib, and antibody-based crizotinib2. The application note, as well as other ATCC angiogenesis research tools, can be found at www.atcc.org/angio