The research team, which includes scientists from Tokyo Metropolitan Komagome Hospital and Hokkaido University in Japan, tested a library of 113 synthetic peptides for their ability to attach to melanoma cells and for their effect on the colonization of melanoma cells in the lung. Those peptides were constructed to match sequences along the laminin α5 globular domain. The scientists observed that the peptideA5G27 competed with laminin α5 in binding to the CD44 receptor at the site of the specific CD44 GAG side chain. A5G27 consists of 13 amino acid residues that are consistent with the laminin α5 sequence extending between residues 2893 and 2904.
Kleinman's colleagues documented the ability of A5G27 to inhibit metastasis of skin cancer cells to the lungs of mice. Furthermore, when melanoma cells were placed under the skin of mice treated with A5G27 synthetic peptides, the cells formed a tumor that was smaller in size and lacking in ample growth of novel blood vessels, compared to the tumors that developed in mice that received no synthetic peptide treatment.
By identifying the peptide that inhibits the laminin α5CD44 interaction from propelling cancer cell migration, invasion and angiogenesis, the research team uncovered a potentially key target for molecular therapy.
More than one million cases of basal cell or squamous cell skin cancers occur annually; melanoma and other non-epithelial skin cancers will cause an estimated 10,250 deaths in 2004.