Functional implication of truncated P-cadherin expression in malignant melanoma.

Cadherins comprise Ca(2+)-dependent homophilic cell-cell adhesion molecules which are responsible for correct location of cells and for tissue integrity. They are crucial factors for the development and maintenance of epithelial architecture. Aberrantly expressed cadherins are known to be involved in malignant transformation of different types of tissues. In a previous study, we determined the expression of a short truncated 50 kDa form of P-cadherin only consisting of the N-terminal part in malignant melanoma. Further analysis revealed that this short 50 kDa form of P-cadherin representing the N-terminal, extracellular region, is secreted by melanoma cells in contrast to the membrane bound form in melanocytes. In order to define the functional relevance of expression of the 50 kDa P-cadherin variant in malignant melanoma, antisense P-cadherin cell clones were generated. The clones in which P-cadherin expression is reduced show no changes in proliferation or in attachment-independent growth when compared to controls. However, a strong reduction of migratory and invasive properties was observed in these cells, suggesting that truncated P-cadherin promotes melanoma cell invasion and migration and therefore has an important role in the progression of malignant melanoma. 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.