Conversion of a2Macroglobulin (a2M) to the fast-form by Wobenzym® interrupts the autocrine loop of TGFb production in melanoma cells
Desser, L., Herbacek, I., Zavadova, E., and Mohr, T.
Institute of Tumorbiology/Cancer Research, University of Vienna, Austria
Proceedings of the American Association for Cancer Research (1999):
40, No. 525.
Integrins are cell surface molecules, which mediate cell-matrix and cell-cell adhesion. TGFb increases av integrin expression on several cell types including melanomas at both, the protein- and mRNA-level. a2M (an inhibitor of proteinases) binds in the fast-form irreversibly TGFb. Wobenzym® (pancreatin, bromelain, papain, trypsin and chymotrypsin) has been successfully used in adjuvant tumor therapy. In this study we examined av integrin expression and TGFb synthesis (ELISA and RT-PCR) in 6 human melanoma cell lines established from primary tumors and metastatic tissues. All cell lines express av integrin and produce TGFb in latent (6/6) or active (3/6) form. Treatment up to 24 hrs with 2ng/ml TGFb enhances av integrin expression in all cell lines investigated. Incubation with Wobenzym® has reduced the expression of av integrins after 8 hrs earliest to 26-66%. This downregulation of av integrins (ELISA) was preceded by a reduction of TGFb mRNA (38-89% of the control). We propose, that Wobenzym® and its constituents reduce the production of TGFb by converting a2M into the fast-form, which binds to TGFb, thus interrupting the autocrine loop of TGFb production.
Datum aktualizace stránky: 19. 1. 2016