Skin Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Skin Cancer, including details on identification, causes, prevention, treatment.

Contact of high-invasive, but not low-invasive, melanoma cells to native collagen I induces the release of mature cathepsin B.

Klose A, Wilbrand-Hennes A, Zigrino P, Weber E, Krieg T, Mauch C, Hunzelmann N

Department of Dermatology, Center for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany.

Metastasis of malignant tumor cells involves cell-cell and cell-matrix interactions, which regulate the expression and localization of proteolytic enzymes. In the present study, we investigated the expression and localization of the lysosomal cysteine proteinase cathepsin B and its natural inhibitors cystatin A, B and C in high- (MV3), intermediate- (SKmel28) and low-invasive (SKmel23, WM164) human melanoma cell lines grown on plastic or in contact with monomeric or fibrillar collagen type I. Neither the transcript levels of cathepsin B nor those of the natural inhibitors, cystatin B and C, were altered by the interaction of melanoma cells with collagen type I. However, protein expression and cellular localization of cathepsin B and its inhibitors were markedly affected. In contrast to low-invasive cells, high-invasive cells constitutively released procathepsin B when cultured on plastic. In addition, contact of invasive cells with fibrillar collagen type I resulted in the release of both mature forms of the protease. Perturbation studies using inhibitory antibodies against the beta1 subunit of the integrin receptor indicated a role for the beta1 integrin receptor family in the regulation of cathepsin B release. Cystatin B protein expression was much lower in high-invasive cells in both culture conditions, when compared to low-invasive cells. Cystatin C expression was comparable in all cells, but cell contact to fibrillar collagen type I induced its expression. These results strongly implicate a pivotal role of cell-matrix interactions for the regulation of cathepsin B localization and activity in melanoma cells.

Published 21 March 2006 in Int J Cancer, 118(11): 2735-43.
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