Adhesion, migration and communication in melanocytes and melanoma.
Under normal conditions, homeostasis determines whether a cell remains quiescent, proliferates, differentiates, or undergoes apoptosis. In this state of homeostasis, keratinocytes control melanocyte growth and behaviour through a complex system of paracrine growth factors and cell-cell adhesion molecules. Alteration of this delicate homeostatic balance and can lead to altered expression of cell-cell adhesion and cell communication molecules and to the development of melanoma. Melanoma cells escape from this control by keratinocytes through three major mechanisms: (1) down-regulation of receptors important for communication with keratinocytes such as E-cadherin, P-cadherin, desmoglein and connexins, which is achieved through growth factors produced by fibroblasts or keratinocytes; (2) up-regulation of receptors and signalling molecules not found on melanocytes but important for melanoma-melanoma and melanoma-fibroblast interactions such as N-cadherin, Mel-CAM, and zonula occludens protein-1 (ZO-1); (3) loss of anchorage to the basement membrane because of an altered expression of the extracellular-matrix binding integrin family. In the current review, we describe the alterations in cell-cell adhesion and communication associated with melanoma development and progression, and discuss how a greater understanding of these processes may aid the future therapy of this disease.
Haass
Nikolas K
NK
The Wistar Institute, Philadelphia, PA 19104, USA.
Smalley
Keiran S M
KS
Li
Ling
L
Herlyn
Meenhard
M
D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008954:Models, Biological; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D015820:Cadherins