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Proteolytic Enzymes Modulate the Adhesion Molecule CD44 on Malignant Cells in Vitro

Gebauer F.,1 Micheel B.,2 Stauder G.,3 Ransberger K.,3 Kunze R.1

1Imtox Inc., Gustav-Meyer-Allee 25, D-13355 Berlin, Germany, 2Institute of Medical Immunology, Charité, Humboldt University Berlin, Luisenstr. 11 -13a, D-10117 Berlin, and the Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, D-13125 Berlin, Germany, 3Medical Enzyme Research Society (MEF), Malvenweg 2, D-82538 Geretsried, Germany.

Int. J. Immunotherapy 1997, Vol. XIII, No. 3/4, pp. 111-119

SO 112 (19-04-2)



 The adhesion molecule CD44 and variants of the molecule on tumor cells are involved in the process of tumor progression and metastasis. We investigated the ability of several proteolytic enzymes to modulate the CD44 molecule on different tumor cell lines. We found that proteolytic enzymes like bromelin, papain, and chymotrypsin were able to modulate CD44 on cells of leukemic origin as well as on melanoma and mammary carcinoma cell lines. We could demonstrate that three different epitopes of CD44 detected by the monoclonal antibodies L-178, J-173, and A3D8 were more or less reduced after enzymatic treatment. The most pronounced effect was found using the plant protease bromelin. But protease treatment did not only reduce the concentration of CD44 epitopes on the surface of tumor cells, the CD44 also mediated adhesion as we were able to show for a cell line derived from a histiocytic lymphoma and for a melanoma cell line (U937 and SK-MEL28). These results imply that treatment with proteolytic enzymes might be useful in reducing the metastatic behavior of malignant cells. Finally, these data are discussed with regard to the potential role of therapeutically used enzymes in future cancer disease therapy.

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