Affiliation:
1. The Wistar Institute, Philadelphia, PA 19104, USA.
Abstract
Reduced gap junction activity has long been implicated in tumorigenesis. To elucidate the potential role of intercellular communication in melanoma development, 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 formation, whereas melanoma cells did not. Instead, melanoma cells communicated among themselves and with fibroblasts. This switch in communication partners coincided with a shift from E-cadherin to N-cadherin expression during melanoma development. Forced expression of E-cadherin by adenoviral gene transfer in N-cadherin-expressing melanoma cells restored gap junctional compatibility with keratinocytes. Our data suggest that (1) melanocyte transformation is associated with loss of the pre-existing gap junctional activity with keratinocytes but a concomitant gain of communication with a newly juxtaposed cell type, the fibroblasts, (2) the specificity of gap junctional formation during melanoma development is determined by the cadherin profile on the melanocytic cells and (3) the overall gap junctional activity of melanocytic cells is not reduced with transformation.
Publisher
The Company of Biologists
Reference58 articles.
1. Gap junctions, electronic coupling, and intercellular communication.;Bennett;Neurosci. Res. Prog. Bull,1978
2. Switch in gap junction protein expression is associated with selective changes in junctional permeability during keratinocytic differentiation.;Brissette;Proc. Natl. Acad. Sci. USA,1994
3. Junctional systems in the pineal gland of the Wistar rat (Ratus ratus). A freeze-fracture and thin section study.;Cieciura;J. Submicrosc. Cytol. Pathol,1991
4. Induction of gap junctional intercellular communication by vitaminD in human skin fibroblasts is dependent on the nuclear vitamin D receptor.;Clairmont;Carcinogenesis,1996
5. Tumor progression and the nature of cancer.;Clark;Brit. J. Cancer,1991
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