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

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