Cadherin repertoire determines partner-specific gap junctional communication during melanoma progression

Reduced gap junction activity has long been implicated in tumorigenesis. To elucidate the potential role of intercellular communication in melanoma de velopment, we examined gap junctional capability of melanocytic cells from various stages of tumor progression in coculture models using dye transfer assays. Normal melanocytes coupled with keratinocytes by gap junctional for mation, whereas melanoma cells did not. Instead, melanoma cells communicate d among themselves and with fibroblasts. This switch in communication partn ers coincided with a shift from E-cadherin to N-cadherin expression during melanoma development. Forced expression of E-cadherin by adenoviral gene tr ansfer in N-cadherin-expressing melanoma cells restored gap junctional comp atibility with keratinocytes. Our data suggest that (1) melanocyte transfor mation is associated with loss of the pre-existing gap junctional activity with keratinocytes but a concomitant gain of communication with a newly jux taposed cell type, the fibroblasts, (2) the specificity of gap junctional f ormation during melanoma development is determined by the cadherin profile on the melanocytic cells and (3) the overall gap junctional activity of mel anocytic cells is not reduced with transformation.