The potential molecular mechanism of overexpression of uPA, IL-8, MMP-7 and MMP-9 induced by TRAIL in pancreatic cancer cell.
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-kappaB 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-kappaB, in pancreatic cancer cells. It points to the necessity to carefully evaluate in vivo side effects of TRAIL.
Zhou
Dong-Hui
DH
Department of Oncology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. zdh19838@hotmail.com
Trauzold
Anna
A
Röder
Christian
C
Pan
Gang
G
Zheng
Cheng
C
Kalthoff
Holger
H
D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics*; D020783:Matrix Metalloproteinase 7 / Q000096:biosynthesis / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis / Q000235:genetics*
D004273:DNA, Neoplasm; D016209:Interleukin-8; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014568:Urokinase-Type Plasminogen Activator; D020783:Matrix Metalloproteinase 7; D020780:Matrix Metalloproteinase 9