Increased Soluble E-Cadherin in Melanoma Patients

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Abstract
Cadherin switching is thought to contribute to melanoma progression. E-cadherin expression is downregulated, facilitating the release of contacts with keratinocytes, while N-cadherin expression is increased, potentially contributing to more migration. Proteolytic cleavage of the cadherin extracellular domain, a process called ectodomain shedding, is one way to decrease cadherin cell surface expression. In addition, the released ectodomain could actively contribute to a more invasive phenotype. To examine if melanoma progression correlates with increased cadherin ectodomain shedding, we tested the presence of N- and E-cadherin extracellular domains in different melanoma cell lines and the presence of E-cadherin in sera of patients. Shedding occurs and is regulated in several melanoma cell lines expressing these cadherins. No correlation could be found between cadherin shedding and invasive capacity of the cell lines. However, we did find a significant increase in serum E-cadherin levels of melanoma patients with advanced disease correlating with increased S100 tumor marker values, suggesting that increased cadherin shedding may contribute to melanoma progression.