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) |
Summary
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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