New Target for Tumor Angiogenesis Inhibition
Researchers led by Dr. Horace DeLisser at the University of Pennsylvania School of Medicine in Philadelphia, PA have found that loss of PECAM-1 (Platelet Endothelial Cell Adhesion Molecule-1) inhibits tumor angiogenesis. They report their data in the August 2009 issue of The American Journal of Pathology.
During angiogenesis, new blood vessels grow from existing blood vessels. Angiogenesis plays a key role in tumor malignancy, but its role in normal growth and development leads to toxicity in anti-angiogenesis cancer therapies.
Antibodies against PECAM-1, a molecule expressed on multiple blood vessel-associated cells, impair blood vessel formation. Cao et al further examined the role of PECAM-1 in angiogenesis using mice that lacked PECAM-1. Tumor angiogenesis was inhibited when endothelial cells, which line blood vessels, did not express PECAM-1, and these PECAM-1-negative endothelial cells had decreased signs of motility, which is important for new blood vessel formation. As PECAM-1 is not required for blood vessel development in the embryo, PECAM-1 may therefore provide a tumor-specific, low toxicity target to inhibit angiogenesis in cancer patients.
Dr. DeLisser and colleagues conclude that “given its potential role in protecting against endotoxic and apoptotic stresses, and as a mediator of leukocyte recruitment, human clinical trials will be required to establish the ultimate safety of therapy targeted against PECAM-1. In this regard, further studies with the goal of specifically defining the role of PECAM-1 as a facilitator of endothelial cell motility will be very important.”
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