Figure 2. Dynamics of cell interactions and communication during melanoma development. (A) In normal human skin, epidermal melanocytes interact with neighboring keratinocytes through E-cadherin and connexins. This contact-dependent interaction is required for the growth and phenotypic control of melanocytes by keratinocytes. (B) A shift of cadherin profile from E- to N- during melanoma development frees the cells from epidermal keratinocytes. (C) Melanoma cells communicate with each other through multiple adhesion or junctional receptors. Besides N-cadherin-mediated adherens junctions and connexin-mediated gap junctions, at least two other adhesion complexes, Mel-CAM and its ligand, L1-CAM and integrin 
vß3, exist in melanoma, both of which are implicated in the progression of melanoma. (D) The cadherin shift confers new adhesive properties. N-cadherin-expressing melanoma cells are able to form N-cadherin-mediated adherens junction and connexin-mediated gap junction with vascular endothelial cells and with (E) fibroblasts.
