By introducing a synthetic peptide that mimics one component of this link, the researchers blocked this cellular interaction, significantly deterring the migration of cancer cells beyond the original tumor site. Blocking this protein linkage also was shown to inhibit angiogenesis--the creation of blood vessels that nourish new, secondary tumors--and spur cell death or apoptosis.
The results, published in the July issue of the journal Cancer Research, open the door to the prospect of targeted therapeutics capable of preventing or limiting the metastasis of skin cancer.
"The ability of these synthetic peptides to reduce tumor cell metastasis and angiogenesis and increase apoptosis may be important in the development of therapeutics for malignancy," said Hynda Kleinman, Ph.D., chief, cell biology section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Md.
As described in their study, the spread of melanoma cancer cells requires the interaction of two proteins, one located on the cell's surface called CD44, and an extracellular matrix protein known as laminin α5.
CD44 is considered a proteogylcan, which is a protein that has lengthy chains of carbohydrates that extend outward from its protein core, giving it a structure similar to a bottle brush. Carbohydrate side chains, called glycosaminoglycans (GAGs), can interact with other molecules outside of the cell wall membrane. CD44 is produced by cells and positioned on their cell surface membrane. It is often overexpressed in cancer cells. Dr. Kleinman and her associates determined that the GAG near one end of the CD44 protein backbone binds to a specific sequence of amino acid residues in laminin α5.
The laminin α5 molecule is an e
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Contact: Russell Vanderboom
vanderboom@aacr.org
215-440-9300
American Association for Cancer Research
15-Jul-2004