139th National Cancer Advisory Board
investigators with varied backgrounds and varied interests. In the FY 2005 House Report 108-636 of the committee that oversees the NCI budget, the committee had been aware of the workshop and encouraged the continued establishment of collaborations and the pursuit of some of the findings of that workshop.
TARP has had notable accomplishments over the past 2 years. It has organized and sponsored the aforementioned workshop on opportunities for cross-discipline collaboration for vascular developmental biology research. A Web site, www.tarp.nih.gov, has been established. New collaborative RFAs, which involve the NIDDK, JDRF, NINDS, NHLBI, NEI, and the NCI, have been initiated. TARP has organized and co-sponsored a Nature Insight publication on angiogenesis, performed a review of the angiogenesis grant portfolios for five member ICs, and convened a panel to review the current angiogenesis portfolio and to offer opinions on new directions and opportunities. Finally, it opened an Angiogenesis Core Facility at the CCR Advanced Technology Center (ATC) in May 2006.
The Angiogenesis Core Facility has as its mission to: (1) validate existing angiogenesis assays and reagents so that investigators can be speaking the same scientific language in various institutions; (2) develop new assays focusing on molecular pathways and systems biology; (3) develop animal models to study the biology of angiogenesis on a molecular or cellular scale; (4) provide clinical trial support to measure changes in angiogenesis in patients on clinical studies; and (5) expand its capabilities over time to provide support services to other investigators. The core facility occupies approximately 1,500 square feet of laboratory space at the Advanced Technology Center where in vitro and in vivo assays can be performed. It operates under the leadership of Dr. Frank Cuttitta, and has a number of investigators who have implemented a number of existing assays, such as the directed In Vivo Angiogenesis Assay, which was developed in the laboratory of Dr. William Stetler-Stevenson.
One of the new assay approaches to measuring angiogenesis involves microvascular endothelial cells. Investigators in the field of vascular biology have been using various preparations of these cells, whether they be from human umbilical veins, so-called HUVECs or dermal or lung microvascular endothelial cells, to study the effects of various agents on angiogenesis, and have assumed that these cells are pure populations of vascular endothelial cells. Dr. Cuttitta and his team in the Core found that most of the commercial preparations that are available to investigators are a mix of both vascular and lymphatic angiogenesis progenitors, endothelial cells that can line both lymphatic and vascular networks. He made the observation by staining some of these commercial preparations and found that up to 20 to 30 percent of the cells are of lymphatic origin based on their LYVE-1 positivity. The receptor profiles on these cells are very different with respect to different VEGF receptor moieties. Dr. Cutitta developed a flow through methodology to separate those agents that affect lymphatic biology by using magnetic beads with antibodies against LYVE-1, as well as beads that are a positive selection, he came up with a flow through that is purely positive for vascular endothelial cells and eliminates the lymphatic cells. Based on the validation of this methodology, Cambrex, which is one of the more common companies that make available endothelial cells, now uses this technology to make available pure populations of vascular endothelial cells for use by investigators across the country.
The facility’s short-term goals aim to standardize investigative approaches by: (1) establishing reliable in vitro and in vivo angiogenesis assays; (2) identifying commercial sources of primary human blood vessel endothelial cells with low lymphatic contamination; and (3) identifying commercial sources of potent angiogenic factors, such as VEGF, to use as standards and respective suppressor compounds for that activity. Long-term goals target bench to bedside applications. These include the development of new in vitro and in vivo angiogenesis and lymph angiogenesis assays, which better mimic the clinical setting, and the modification of existing assays to measure patient endpoints when patients are on pro or antiangiogenic therapies. The identification of new angiogenic, both anti and pro, as well as lymphangiogenic drugs using established assays is a further objective. Finally, the facility aims to serve