The role of genetic instability, adhesion, cell motility, and immune escape mechanisms in melanoma progression.
Advances in different fields of research have recently contributed to the understanding of melanoma progression. Genetic instability and mutations of putative melanoma susceptibility genes are key factors involved in increased melanoma risk. The identification of the responsible loci and genes by karyotyping and genetic linkage analysis of tumors, affected individuals, and their families will allow further insight into molecular mechanisms of melanoma development. One susceptibility gene is located on chromosome 9p21. Changes in adhesiveness and cell motility are important for tumor progression and may even represent prime factors determining aggressiveness and metastatic potential. In melanoma, several adhesion receptors of the integrin family (eg, alpha V beta 3, alpha 4 beta 1, alpha 2 beta 1) and the CD44 receptor are potentially relevant in this process. Several mechanisms appear to be involved in the escape of melanoma from immunologic control, 1) downregulation of surface-expressed major histocompatibility complex class I molecules and the failure of tumor cells to process endogenously synthesized proteins for antigen presentation, 2) inhibition of the interaction of cytotoxic T cells with melanoma cells, eg, by soluble adhesion molecules (intercellular adhesion molecule 1), and 3) induction and maintenance of clonal anergy in tumor cell-specific T cells.
Rünger
T M
TM
Department of Dermatology, University of Würzburg, Germany.
Klein
C E
CE
Becker
J C
JC
Bröcker
E B
EB
D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000032:analysis; D002465:Cell Movement; D006684:HLA-DR Antigens / Q000032:analysis; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D008545:Melanoma / Q000209:etiology* / Q000235:genetics / Q000276:immunology
D015815:Cell Adhesion Molecules; D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I; D018799:Intercellular Adhesion Molecule-1