A secreted form of P-cadherin is expressed in malignant melanoma

Cadherins are Ca-dependent homophilic cell-cell adhesion molecules which are responsible for correct location of cells and tissue integrity. They are critical for development and maintenance of epithelial architecture. Aberrantly expressed cadherins are known to be involved in malignant transformation of different types of tissues. In this study, we show the expression of a short truncated 50 kDa form of the N-terminal part of P-cadherin in seven melanoma cell lines compared to melanocytes and keratinocytes. In vitro protein analysis on cell culture supernatant as well as immunohistochemistry of primary and metastatic melanoma tissue revealed the expression of this short form of P-cadherin. Furthermore, analysis showed that this short 50 kDa form of P-cadherin is secreted by melanoma cells in contrast to the membrane bound form in melanocytes. Analysis on mRNA level detected only exon 1 to 10 of P-cadherin resulting in the 50 kDa form missing the transmembrane and cytoplasmatic region. Genomic sequence analysis did not show any mutations in melanoma cells neither in the exons nor in the exon-intron boundaries. Furthermore, there was no loss of exons 11-16 on the genomic level. Functionally, the secreted form of P-cadherin could play a role as regulator of the homophilic interaction between P-cadherin molecules by antagonizing their biological role acting as a dominant negative form to interrupt cell-cell attachment.