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| 1 | The potential molecular mechanism of overexpression of uPA, IL-8, MMP-7 and MMP-9 induced by TRAIL in pancreatic cancer cell显示文摘BACKGROUND:TNF-related apoptosis-inducing ligand (TRAIL) is a death ligand of the TNF-superfamily that has been implicated in inducing apoptosis in some tumor cells. The purpose of this study was to find out if TRAIL could induce the expression of uPA, IL-8, MMP-7 and MMP-9. and to explore the corresponding potential signaling transduction pathway in pancreatic cancer cells. METHODS:Colo357wt, Panc89 and PancTuⅠ cell lines were stimulated by TRAIL (100 ng/ml). Crystal violet cell vitality assay was used to check the sensitivity to TRAIL-induced apoptosis. Real-time RT-PCR tested the expression of uPA, IL-8, MMP-7 and MMP-9. RESULTS:TRAIL can stimulate the expression of uPA, IL-8, MMP-7 and MMP-9 in pancreatic cancer cell lines, especially in Colo357wt. The members of caspases, MEK1/2, PKC, and NF-κB are involved in TRAIL-induced expression of uPA, IL-8, MMP-7 and MMP-9. Furthermore, caspases play a different role in Colo357wt, Panc89 and PancTuⅠ. CONCLUSIONS:TRAIL-treatment may result in the enhancement of invasion involving the signaling pathways of caspases, MEK1/2, PKC and NF-κB, in pancreatic cancer cells. It points to the necessity to carefully evaluate in vivo side effects of TRAIL. | Anna Trauzold Christian Rder Holger Kalthoff | 2008 | Hepatobiliary & Pancreatic Diseases International2008，7，2： | 6 |
| 2 | TRAIL-induced expression of uPA and IL-8 strongly enhanced by overexpression of TRAF2 and Bcl-xL in pancreatic ductal adenocarcinoma cells显示文摘BACKGROUND:The death ligand,tumor necrosis factor(TNF)related apoptosis-inducing ligand(TRAIL),induces apoptosis and non-apoptotic signaling in some tumor cells.The purpose of this study was to investigate the roles of the pro-apoptotic TRAIL receptors,TRAIL-R1 and TRAIL-R2,as well as Bcl-xL and TRAF2 in TRAIL-induced expression of the pro-inflammatory cytokine IL-8 and the invasion-promoting protein urokinase(uPA) in pancreatic ductal adenocarcinoma(PDAC) cells.METHODS:Colo357wt,Colo357/TRAF2,Colo357/Bcl-xL,Panc89 and PancTuI cells were stimulated with TRAIL and uPA and IL-8 expression was detected using real-time PCR.Antagonistic,receptor-specific antibodies were used to investigate the effects of TRAIL-R1 or TRAIL-R2 inhibition.RESULTS:Dose-dependent increases in uPA and IL-8 expression were detected following TRAIL stimulation in PDAC cells.These effects were inhibited when TRAIL-R1 but not TRAIL-R2 was blocked.Overexpression of TRAF2 or Bcl-xL strongly increased TRAIL-mediated upregulation of uPA and IL-8.CONCLUSIONS:In PDAC cells,TRAIL strongly induced uPA and IL-8 via TRAIL-R1.This response was further enhanced in cells overexpressing TRAF2 and Bcl-xL.Therefore,inhibition of the non-apoptotic 'side-effects' of TRAIL treatments by inactivation of TRAF2 and Bcl-xL might represent additional relevant strategies for the treatment of pancreatic cancer. | Dong-Hui Zhou Li-Na Yang Christian Rder Holger Kalthoff Anna Trauzold | 2013 | Hepatobiliary & Pancreatic Diseases International2013，12，1： | 5 |
| 3 | Topology impacts TRAIL therapy: Differences in primary cancer growth and liver metastasis between orthotopic and subcutaneous xenotransplants of pancreatic ductal adenocarcinoma cells显示文摘Background: To study novel treatment modalities for pancreatic ductal adenocarcinoma(PDAC), we need to transfer the knowledge from in vitro to in vivo. It is important to mirror the clinical characteristics of the typically local invasive growth of pancreatic cancer and the distant spread resulting in liver metastasis. Notably, for xenotransplant studies using human specimen, two models, i.e. subcutaneous(s.c.) and orthotopic(o.t.) transplantation are widely used. Methods: The subcutaneously and orthotopically inoculated Colo357 Bcl-x L cell-derived tumors were directly compared with and without TNF-related apoptosis inducing ligand(TRAIL) treatment. The size of primary tumors, number of liver metastasis and the histologic markers Ki67, M30, TNF-α and CD31 were assessed. Results: Upon TRAIL treatment, the primary tumors did not change their size, neither in the s.c. nor in the o.t. approaches. But when s.c. was compared to o.t., the size of the s.c. tumors was more than twofold bigger than that of the o.t. tumors( P<0.01). However, mice with orthotopically inoculated PDAC cells developed liver metastasis upon TRAIL treatment much more frequently( n=13/17) than mice with subcutaneously inoculated PDAC cells( n=1/11)( P<0.01). As a likely driving force for this increased metastasis, a higher TNF-α staining intensity in the o.t. tumors was observed by immunohistochemistry. Conclusions: These data from a direct side-by-side comparison underline the importance of the proper inoculation site of the PDAC cells. Local invasion and liver metastases are a hallmark of PDAC in the clinic;the o.t. model is clearly superior in reflecting this setting. Moreover, a serious side-effect of a possible new therapeutic compound became obvious only in the o.t. model. | Bastian Kettler Anna Trauzold Christian Röder Jan-Hendrik Egberts Holger Kalthoff | 2021 | Hepatobiliary & Pancreatic Diseases International2021，20，3： | 3 |
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