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

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 β1 subunit of the integrin receptor indicated a role for the β1 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. © 2005 Wiley‐Liss, Inc.