Cell-surface proteolysis, growth factor activation and intercellular communication in the progression of melanoma

https://doi.org/10.1016/S1040-8428(01)00196-2Get rights and content

Abstract

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 a 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.

Keywords

Melanoma
Proteolysis
Microenvironment
Stroma
Cell-surface peptidases
Ephrins
Eph receptors

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Thomas Bogenrieder attended Medical School in Homburg/Saar and Freiburg, Germany, and Strasbourg, France, from 1985 to 1992. He received postdoctoral training in the laboratory of Dr A. Albino at Memorial Sloan-Kettering Cancer Center in New York, 1993–1995. He was a Resident in Dermatology and Allergology at the University of Regensburg Medical Center, Germany, from 1995 to 2000. Presently, he is a Visiting Scientist in the laboratory of Dr M. Herlyn at the Wistar Institute in Philadelphia. His major academic interest is melanoma.

Meenhard Herlyn received his D.V.M. from the University of Hannover, Germany, in 1970. Between 1970 and 1976 he worked as a Postdoctoral Fellow and Assistant in Immunology and Microbiology at the University of Munich, Germany. In 1976, he came to the Wistar Institute in Philadelphia as an Associate Scientist in the laboratory of Dr H. Koprowski. In 1981, he was appointed Assistant Professor, 1986 Associate Professor and in 1991 Professor at Wistar. Since 1996, he is Chairman of the Tumor Biology Program. He has worked on various aspects of melanoma biology for the last 25 years.

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