July 23, 2009

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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American Journal of Pathology