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Scientists find blood vessel-building protein halts blood vessels from forming in cancer

A piece of the protein cellular scaffolding involved in building blood vessels during development might have the opposite effect in tumors.

Cell biologists at Jefferson Medical College and the Kimmel Cancer Center of Thomas Jefferson University in Philadelphia have found that the protein fragment endorepellin blocks both skin and lung cancer tumors from progressing in animal models by preventing their ability to recruit new blood vessels, a process called angiogenesis. They showed that endorepellin has surprisingly powerful effects on halting a cancer tumor's ability to move about and spread.

The researchers believe that these latest findings, appearing November 15, 2006 in the Journal of the National Cancer Institute, could lead to a new type of tumor inhibitor that might be used to prevent cancer from spreading to other areas in the body.

The researchers, led by Renato Iozzo, M.D., professor of pathology, anatomy and cell biology at Jefferson Medical College of Thomas Jefferson University, used two animal models of cancer to study squamous cell carcinoma and lung carcinoma. When they injected animals with artificially created "recombinant" endorepellin, they discovered that it blocked tumor growth, metabolism and angiogenesis. They also found for the first time that endorepellin targets the tumor endothelial cells, blocking the creation of new blood vessels.

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"These findings have major implications for cancer treatments for a range of solid tumors such as lung, prostate and breast," Dr. Iozzo says. "All of these tumors depend on angiogenesis, so we think this could be an effective adjuvant therapy for cancer."

Endorepellin is part of the protein perlecan, which plays fundamental roles in vascular biology as scaffolding for blood vessel formation in development. In cancer, perlecan not only regulates growth factor activity, but also is a barrier to invading cancer cells.

Anti-angiogenesis drugs were all the rage in the late 1990s, when animal studies showed two drugs seemingly "melting" tumors in mice. But disappointing human clinical trials since then have scaled back expectations, and most now see such drugs as part of a treatment milieu that includes surgery, chemotherapy and radiation. More recent study results, however, Dr. Iozzo says, have renewed interest in the drugs' potential.

Dr. Iozzo says that these results suggest that endorepellin might be used to help prevent metastatic cancer spread in patients who have had a primary tumor removed. "It could be used preventatively and for maintenance, and in combination with other drugs," he notes.

"While endorepellin prevents the formation of the original blood vessels in tumor development, I think it would be more effectively used after the tumor has formed and cells try to migrate and spread," Dr. Iozzo says. The researchers are hoping to begin clinical testing of endorepellin in the near future.

Steve Benowitz | EurekAlert!
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