Disconnecting Cancer Cells
Posted January 18, 2008, 4:07 PM EST
Cut yourself or scrape your elbow, and your body automatically steps in to heal the damage. Specialized infection-fighting cells arrive on the scene, and once the area is secured, new cells are pressed into service to replace dead tissue. Through a process called angiogenesis, these new cells are connected to your circulatory system so they can receive the nutrients they need to flourish.
In the proper context, angiogenesis is fundamental to life, playing a critical role in embryonic development as well as wound healing. However, when cells slip beyond the body’s regulatory control and become cancerous, they harness angiogenesis for their own ends, in essence securing their survival by generating their own blood supply. “If we can find substances implicated in producing angiogenesis,” says Carol Rivera-Lopez, graduate student in molecular medicine and systems biology-pharmacology, “we can find ways to block it, thus starving the cancer cells that depend on it.”
Blocking angiogenesis, however, is not a simple matter because of the body’s penchant for redundancy. There are a number of substances that are known to stimulate the formation of capillaries, including vascular endothelial growth factor (VEGF), a protein that has been the subject of many experiments. With Professor Kevin Lynch in the Department of Pharmacology, Rivera-Lopez is examining another substance implicated in angiogenesis called lysophosphatidic acid (LPA). Her work has been funded by a National Research Service Award from the National Institutes of Health.
Working with chicken embryos, Rivera-Lopez found that LPA encouraged the growth of new blood vessels that were more fully articulated than blood vessels stimulated by VEGF. Having established this fact, she experimented with molecules developed by faculty members in the Department of Chemistry that block two of the receptors for LPA. The results were dramatic: these LPA antagonists completely prevented capillary formation.
Rivera-Lopez’s next step was to move to an experimental platform that has more in common with people—the mouse. Using specialized “knock-out” mice that are bred to have only a specific type of LPA receptor, Rivera-Lopez hopes to identify the LPA receptor most closely associated with angiogenesis in cancer cells.
Rivera-Lopez, who is from Puerto Rico, got her first taste of research at U.Va. during a ten-week summer internship program in the Department of Biochemistry. Her mentor in the department urged her to consider graduate school, and when she did, U.Va. was her first choice. “I was very impressed by the spirit of collaboration I found here,” she says. “Faculty members have gone out of their way to help me, opening doors and making introductions, providing access to their equipment, and helping me refine my disease model. It’s a great environment.”