Dataset Information
Inhibiting tumor necrosis factor-alpha diminishes desmoplasia and inflammation to overcome chemoresistance in pancreatic ductal adenocarcinoma.
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ABSTRACT: Background
Pancreatic ductal adenocarcinoma (PDAC) is one of the most common cancer death reasons. Anti-tumor necrosis factor-alpha (TNF-?) antibodies have shown promising effects in PDAC pre-clinical models. However, the prognostic values of TNF-?, underlying mechanisms by which anti-TNF-? treatments inhibit PDAC, and potential synergistic effects of anti-TNF-? treatments with chemotherapy are still unclear.Results and methods
To identify the targeting values of TNF-? in PDAC, we measured TNF-? expression in different stages of PDAC initiation and evaluated its prognostic significance in a pancreatic cancer cohort. We found that TNF-? expression elevated in PDAC initiation process, and high expression of TNF-? was an independent prognostic marker of poor survival. We further evaluated anti-tumor effects of anti-TNF-? treatments in PDAC. Anti-TNF-? treatments resulted in decreased cell viability in both PDAC tumor cells and pancreatic satellite cells in similar dose in vitro. In vivo, anti-TNF-? treatments showed effects in reducing desmoplasia and the tumor promoting inflammatory microenvironment in PDAC. Combination of anti-TNF-? treatments with chemotherapy partly overcame chemoresistance of PDAC tumor cells and prolonged the survival of PDAC mouse model.Conclusions
In conclusion, our findings indicated that TNF-? in PDAC can be a prognostic and therapeutic target. Inhibition of TNF-? synergized with chemotherapy in PDAC resulted in better pre-clinical responses via killing tumor cells as well as diminishing desmoplasia and inflammation in PDAC tumor stroma.
SUBMITTER: Zhao X
PROVIDER: S-EPMC5348380 | biostudies-literature | 2016 Dec
REPOSITORIES: biostudies-literature
Publications
Inhibiting tumor necrosis factor-alpha diminishes desmoplasia and inflammation to overcome chemoresistance in pancreatic ductal adenocarcinoma.
Oncotarget 20161201 49
<h4>Background</h4>Pancreatic ductal adenocarcinoma (PDAC) is one of the most common cancer death reasons. Anti-tumor necrosis factor-alpha (TNF-α) antibodies have shown promising effects in PDAC pre-clinical models. However, the prognostic values of TNF-α, underlying mechanisms by which anti-TNF-α treatments inhibit PDAC, and potential synergistic effects of anti-TNF-α treatments with chemotherapy are still unclear.<h4>Results and methods</h4>To identify the targeting values of TNF-α in PDAC, w ...[more]
