Journal
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
Volume 44, Issue 1, Pages 1-15Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/S1040-8428(01)00196-2
Keywords
melanoma; proteolysis; microenvironment; stroma; cell-surface peptidases; ephrins; Eph receptors
Categories
Funding
- NCI NIH HHS [R01 CA080999, P01 CA025874, CA47159, R01 CA076674, CA80999, CA25874, R01 CA047159, CA76674] Funding Source: Medline
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Normal skin architecture and melanocyte function is maintained by a dynamic interplay between the melanocytes themselves, the epithelial cells between which they are interspersed, and their microenvironment. The microenvironment consists of the extracellular matrix, fibroblasts, migratory immune cells, and neural elements supported by Vascular network. all within a milieu of cytokines, growth factors, and bioactive peptides as well as proteolytic enzymes. Cells interact with the microenvironment via complex autocrine and paracrine mechanisms. Proteolytic enzymes in melanoma may activate or release growth factors from the microenvironment or act directly on the microenvironment itself, thereby facilitating angiogenesis or tumor cell migration. This review summarizes recent findings regarding the expression, structure and function of proteolytic enzymes at or near the cell surface in cell-cell and cell-stroma interactions during melanoma progression. Cell-surface (membrane) peptidases are a multi-functional group of ectoenzymes that have been implicated in the control of growth and differentiation of many cellular systems. The potential, but yet speculative, role of other membrane-bound molecules. such as multifunctional Surface proteins with adhesion and protease activity (ADAM gene family) or the ephrin Eph receptor protein kinases in the pathogenesis of melanoma are discussed. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
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