Polyenzyme preparations interrupt the autocrine loop of TGFb production in melanoma cells by conversing a2Macroglobulin (a2M) into the fast-form which binds TGF-beta irreversible 

Desser, L., Herbacek, I., Zavadova, E., and Mohr, T.

Institute of Tumorbiology/Cancer Research, University of Vienna, Austria

The European Cancer Conference, Vienna 12. -16. Sept. 1999, Enzyme forum ECCO 10, abs. 3
published in The European Journal of Cancer 1999; Vol. 35, Suppl. 4, poster 1526, pp. 375.

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

90th Annual Meeting  April 10 - 14, 1999 - Philadelphia. 
Published in American Association for Cancer Research, Vol. 40, March 1999, Poster 525

491 KA (2-08-1)

Czech version available here.

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.