Melanoma, the most aggressive form of
skin cancer, which accounts for 75% of all
skin cancer-related deaths, continues to rise at an alarming rate worldwide. Despite a favorable cure rate when surgically removed at an early stage, the response rate of patients with metastatic disease to single agent
chemotherapy is less than 15%, and
biologic therapies are only marginally effective. Given this bleak picture, there is a great need to identify and characterize genes that play an important role in the advanced stages of
melanoma and thus, may represent valuable targets for clinical
therapy. The
cell adhesion molecules N-cadherin, MCAM and
beta3 integrin have been suggested to represent
melanoma progression markers; yet, little is known as to whether they may constitute therapeutic targets for the disease. To provide information regarding this aspect, we determined by way of whole-genome and tissue microarray analysis, their level of expression concordant with
melanoma progression, and via RNA interference and antisense technology, their role in
melanoma cell proliferation, migration, and invasion. The results of these studies demonstrate that
N-cadherin and
beta3 integrin expression correlates with progression to advanced-stage
melanoma, whereas expression of MCAM does not. On the other hand, MCAM and
beta3 integrin are the two adhesion molecules that play a pivotal role in
melanoma cell migration and invasion, and for this reason, may represent valuable targets for
melanoma therapy.