Processing of Immunosuppressive Pro-TGF-β1,2 by Human Glioblastoma Cells Involves Cytoplasmic and Secreted Furin-Like Proteases | Zendy

Jens Leitlein | Zendy; Steffen Aulwurm | Zendy; Robert Waltereit | Zendy; Ulrike Naumann | Zendy; Bettina Wagenknecht | Zendy; Wolfgang Garten | Zendy; Michael Weller | Zendy; Michael Platten | Zendy

Open Access

Processing of Immunosuppressive Pro-TGF-β1,2 by Human Glioblastoma Cells Involves Cytoplasmic and Secreted Furin-Like Proteases

Author(s) -

Jens Leitlein,

Steffen Aulwurm,

Robert Waltereit,

Ulrike Naumann,

Bettina Wagenknecht,

Wolfgang Garten,

Michael Weller,

Michael Platten

Publication year - 2001

Publication title -

the journal of immunology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.737

H-Index - 372

eISSN - 1550-6606

pISSN - 0022-1767

DOI - 10.4049/jimmunol.166.12.7238

Subject(s) - furin , proprotein convertases , glioma , proprotein convertase , proteases , cell culture , kexin , chemistry , biology , microbiology and biotechnology , cancer research , biochemistry , enzyme , lipoprotein , genetics , ldl receptor , cholesterol

TGF-beta is a putative mediator of immunosuppression associated with malignant glioma and other types of cancer. Subtilisin-like proprotein convertases such as furin are thought to mediate TGF-beta processing. Here we report that human malignant glioma cell lines express furin mRNA and protein, exhibit furin-like protease (FLP) activity, and release active furin into the cell culture supernatant. FLP activity is not modulated by exogenous TGF-beta or neutralizing TGF-beta Abs. Exposure of LN-18 and T98G glioma cell lines to the furin inhibitor, decanoyl-Arg-Val-Lys-Arg-chloromethylketone, inhibits processing of the TGF-beta1 and TGF-beta2 precursor molecules and, consequently, the release of mature bioactive TGF-beta molecules. Ectopic expression of PDX, a synthetic antitrypsin analog with antifurin activity, in the glioma cells inhibits FLP activity, TGF-beta processing, and TGF-beta release. Thus, subtilisin-like proprotein convertases may represent a novel target for the immunotherapy of malignant glioma and other cancers or pathological conditions characterized by enhanced TGF-beta bioactivity.

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