Influence of Protease Treatment on the Adhesiveness of Tumor Cells to Extracellular Matrix Components

Author(s): Erdmann, F. -C., Rimpler, M.

Abstract: The ability of malignant tumor cells to form secondary lesions depends on multiple adhesive steps during invasion and metastasis. Details are given that a proteolytic treatment of the tumor cell surface causes a decreased attachment of the cells to matrix components.The attachment of murine B16 melanoma cells to the complete matrix (ECM) showed 40% inhibition after a bromelain treatment in comparison to control cells. A reduced binding rate to the isolated matrix components laminin and fibronectin was also found for the melanoma cell line as well as for a human bladder carcinoma (BC) after a proteolytic treatment with bromelain or ficin. Furthermore, the haptotactic migration of pancreatic carcinoma cells (DAN-G cell line) to laminin and fibronectin and that of B16-Fl cells to fibronectin was also influenced by ficin and bromelain, as shown in an in vitro invasion system.Other experiments were performed with arg-gly-asp-containing synthetic peptides (RGD polymer) as attachment protein mimicking the cell-binding domain of many adhesive proteins, which is recognized by several cell surface receptors.A bromelain treatment reduced the RGD attachment of B16 melanoma cells and that of their B16-Fl and B16-F10 variants, which differ in their capacity to colonize the lung.A panel of other proteases, including human elastase and plasmin, assayed in a physiological concentration, showed a similiar adhesion-reducing effect. The chromatographic purification of bromelain resulted in fractions which only influenced the cell binding to the adhesive sequence in a lower extent than the starting material.The ability of the tested proteases to reduce the cell binding to the RGD polymer indicates an influence of the proteolytic treatment on the RGD-dependent integrin system.The findings support the possibility for a therapeutic use of proteases for adjuvant cancer treatment.

Keyword(s): Metastasierung

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