title: Cell adhesion molecules in the development and progression of malignant melanoma.
abstract: Cell adhesion molecules belonging to the integrin, cadherin and immunoglobulin superfamilies have been implicated in tumor progression in cutaneous melanoma. Expression of the alpha v beta 3 integrin first appears with the change from radial to vertical growth, a step which is associated with the development of metastatic potential. VLA-4 expression is characteristic of advanced primary tumors and may mediate interaction of the tumor cells with VCAM-1 on vascular endothelium. Expression of these integrins is a marker of poor prognosis in patients and can confer invasive (alpha v beta 3) and metastatic (VLA-4) properties to human melanoma cells injected into nude mice. Expression of the immunoglobulin superfamily molecules MUC18/MCAM and ICAM-1 are associated with primary tumors and metastases. MUC18/MCAM expression confers metastatic potential and increased tumorigenicity to human melanoma cells. Expression of ICAM-1 has been shown to be a marker of poor prognosis in stage I tumors and interfering with its expression inhibits experimental metastasis by melanomas in nude mice. E-cadherin is used by epidermal melanocytes to interact with neighboring keratinocytes. Changes in E-cadherin expression and cellular localization is first observed in the radial growth phase, the earliest stage in melanoma development. Loss of E-cadherin function is associated with upregulation or induction of MUC18/MCAM and alpha v beta 3 in melanocytic cells in vitro and with alterations in the levels and cellular distribution of the transcriptional regulator beta-catenin in melanomas in vivo. These observations suggest that disturbances in E-cadherin function is not only important in carcinomas but may also be a critical event in melanoma tumor progression.
authors.affiliation: Institute for Immunology, University of Munich, Germany. johnson@ifi.med.uni-muenchen.de
authors.forename: J P
authors.initials: JP
authors.lastname: Johnson
mesh_terms: D000818:Animals; D015703:Antigens, CD; D051929:CD146 Antigen; D015820:Cadherins / Q000032:analysis / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000502:physiology; D008545:Melanoma / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D019006:Neural Cell Adhesion Molecules; D016201:Receptors, Lymphocyte Homing / Q000502:physiology
chemical_list: D015703:Antigens, CD; D051929:CD146 Antigen; D015820:Cadherins; D015815:Cell Adhesion Molecules; D039041:Integrin alpha4beta1; D016023:Integrins; C497902:MCAM protein, human; C497903:Mcam protein, mouse; D008562:Membrane Glycoproteins; D019006:Neural Cell Adhesion Molecules; D016201:Receptors, Lymphocyte Homing