%0 Journal Article
%T Transforming growth factor-汕1 blocks the enhancement of tumor necrosis factor cytotoxicity by hyaluronidase Hyal-2 in L929 fibroblasts
%A Nan-Shan Chang
%J BMC Cell Biology
%D 2002
%I BioMed Central
%R 10.1186/1471-2121-3-8
%X Murine L929 fibroblasts were engineered to stably express green-fluorescent protein (GFP)-tagged hyaluronidase (GFP-Hyal-1 or GFP-Hyal-2) or GFP alone. Compared to control cells, Hyal-2-expressing cells had a significantly increased sensitivity to TNF cytotoxicity (~60每110% increase), while Hyal-1-expressing cells were less sensitive to TNF (~20每90% increase). TNF activated NF-百B, along with I百B汐 degradation, occurred at 20 to 60 min in Hyal-2 cells post stimulation, but at the 20 min time point in both control and Hyal-1 cells. Hyal-2 cells, but not Hyal-1 and control cells, constitutively expressed WOX1, and transiently expressed Hyal-2 enhanced WOX1-mediated cell death. Unlike PH-20, Hyal-1 and Hyal-2 did not induce p53 expression. Hyal-2 translocated from the lysosome to the mitochondria during staurosporine-mediated apoptosis, suggesting that Hyal-2 may damage mitochondria. Finally, Hyal-1 and Hyal-2 blocked TGF-汕1-enhanced L929 cell growth. In contrast, TGF-汕1 inhibited Hyal-1- and Hyal-2-increased TNF cytotoxicity in L929 cells by 30每50%.TGF-汕1 limits the ability of Hyal-2 to induce TNF cytotoxicity in L929 cells. Hyal-2-increased TNF cytotoxicity in L929 cells appears to be correlated with upregulation of WOX1, a prolonged NF-百B activation, and Hyal-2 translocation to the mitochondria during apoptosis.Transforming growth factor beta (TGF-汕) family proteins are multifunctional cytokines capable of regulating cell growth, extracellular matrix protein synthesis, and immune cell functions [1,2]. Hyaluronidase is an extracellular matrix-degrading enzyme. Interestingly, malignant and metastatic breast and prostate cancer cells frequently overexpress both hyaluronidase and TGF-汕 proteins [3-7]. Previously we have shown that bovine testicular hyaluronidase, also known as PH-20, increases the susceptibility of various cancer cells to tumor necrosis factor (TNF or TNF-汐) cytotoxicity [[8], review]. PH-20 induces the expression of proapoptotic p53 [9] and WOX1 (WW doma
%U http://www.biomedcentral.com/1471-2121/3/8