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The Hepatic Microenvironment and TRAIL-R2 Impact Outgrowth of Liver Metastases in Pancreatic Cancer after Surgical Resection

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The Hepatic Microenvironment and TRAIL-R2 Impact Outgrowth of Liver Metastases in Pancreatic Cancer after Surgical Resection. / Miarka, Lauritz; Hauser, Charlotte; Helm, Ole; Holdhof, Dörthe; Beckinger, Silje; Egberts, Jan-Hendrik; Gundlach, Jan-Paul; Lenk, Lennart; Rahn, Sascha; Mikulits, Wolfgang; Trauzold, Anna; Sebens, Susanne.

in: CANCERS, Jahrgang 11, Nr. 6, 29.05.2019.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Miarka, L, Hauser, C, Helm, O, Holdhof, D, Beckinger, S, Egberts, J-H, Gundlach, J-P, Lenk, L, Rahn, S, Mikulits, W, Trauzold, A & Sebens, S 2019, 'The Hepatic Microenvironment and TRAIL-R2 Impact Outgrowth of Liver Metastases in Pancreatic Cancer after Surgical Resection', CANCERS, Jg. 11, Nr. 6. https://doi.org/10.3390/cancers11060745

APA

Miarka, L., Hauser, C., Helm, O., Holdhof, D., Beckinger, S., Egberts, J-H., Gundlach, J-P., Lenk, L., Rahn, S., Mikulits, W., Trauzold, A., & Sebens, S. (2019). The Hepatic Microenvironment and TRAIL-R2 Impact Outgrowth of Liver Metastases in Pancreatic Cancer after Surgical Resection. CANCERS, 11(6). https://doi.org/10.3390/cancers11060745

Vancouver

Miarka L, Hauser C, Helm O, Holdhof D, Beckinger S, Egberts J-H et al. The Hepatic Microenvironment and TRAIL-R2 Impact Outgrowth of Liver Metastases in Pancreatic Cancer after Surgical Resection. CANCERS. 2019 Mai 29;11(6). https://doi.org/10.3390/cancers11060745

Bibtex

@article{2221d88874d642258152722ca827be8d,
title = "The Hepatic Microenvironment and TRAIL-R2 Impact Outgrowth of Liver Metastases in Pancreatic Cancer after Surgical Resection",
abstract = "Most patients with pancreatic ductal adenocarcinoma (PDAC) undergoing curative resection relapse within months, often with liver metastases. The hepatic microenvironment determines induction and reversal of dormancy during metastasis. Both tumor growth and metastasis depend on the Tumor necrosis factor (TNF)-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2). This study investigated the interplay of TRAIL-R2 and the hepatic microenvironment in liver metastases formation and the impact of surgical resection. Although TRAIL-R2-knockdown (PancTu-I shTR2) decreased local relapses and number of macroscopic liver metastases after primary tumor resection in an orthotopic PDAC model, the number of micrometastases was increased. Moreover, abdominal surgery induced liver inflammation involving activation of hepatic stellate cells (HSCs) into hepatic myofibroblasts (HMFs). In coculture with HSCs, proliferation of PancTu-I shTR2 cells was significantly lower compared to PancTu-I shCtrl cells, an effect still observed after switching coculture from HSC to HMF, mimicking surgery-mediated liver inflammation and enhancing cell proliferation. CXCL-8/IL-8 blockade diminished HSC-mediated growth inhibition in PancTu-I shTR2 cells, while Vascular Endothelial Growth Factor (VEGF) neutralization decreased HMF-mediated proliferation. Overall, this study points to an important role of TRAIL-R2 in PDAC cells in the interplay with the hepatic microenvironment during metastasis. Resection of primary PDAC seems to induce liver inflammation, which might contribute to outgrowth of liver metastases.",
keywords = "Journal Article",
author = "Lauritz Miarka and Charlotte Hauser and Ole Helm and D{\"o}rthe Holdhof and Silje Beckinger and Jan-Hendrik Egberts and Jan-Paul Gundlach and Lennart Lenk and Sascha Rahn and Wolfgang Mikulits and Anna Trauzold and Susanne Sebens",
year = "2019",
month = may,
day = "29",
doi = "10.3390/cancers11060745",
language = "English",
volume = "11",
journal = "CANCERS",
issn = "2072-6694",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "6",

}

RIS

TY - JOUR

T1 - The Hepatic Microenvironment and TRAIL-R2 Impact Outgrowth of Liver Metastases in Pancreatic Cancer after Surgical Resection

AU - Miarka, Lauritz

AU - Hauser, Charlotte

AU - Helm, Ole

AU - Holdhof, Dörthe

AU - Beckinger, Silje

AU - Egberts, Jan-Hendrik

AU - Gundlach, Jan-Paul

AU - Lenk, Lennart

AU - Rahn, Sascha

AU - Mikulits, Wolfgang

AU - Trauzold, Anna

AU - Sebens, Susanne

PY - 2019/5/29

Y1 - 2019/5/29

N2 - Most patients with pancreatic ductal adenocarcinoma (PDAC) undergoing curative resection relapse within months, often with liver metastases. The hepatic microenvironment determines induction and reversal of dormancy during metastasis. Both tumor growth and metastasis depend on the Tumor necrosis factor (TNF)-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2). This study investigated the interplay of TRAIL-R2 and the hepatic microenvironment in liver metastases formation and the impact of surgical resection. Although TRAIL-R2-knockdown (PancTu-I shTR2) decreased local relapses and number of macroscopic liver metastases after primary tumor resection in an orthotopic PDAC model, the number of micrometastases was increased. Moreover, abdominal surgery induced liver inflammation involving activation of hepatic stellate cells (HSCs) into hepatic myofibroblasts (HMFs). In coculture with HSCs, proliferation of PancTu-I shTR2 cells was significantly lower compared to PancTu-I shCtrl cells, an effect still observed after switching coculture from HSC to HMF, mimicking surgery-mediated liver inflammation and enhancing cell proliferation. CXCL-8/IL-8 blockade diminished HSC-mediated growth inhibition in PancTu-I shTR2 cells, while Vascular Endothelial Growth Factor (VEGF) neutralization decreased HMF-mediated proliferation. Overall, this study points to an important role of TRAIL-R2 in PDAC cells in the interplay with the hepatic microenvironment during metastasis. Resection of primary PDAC seems to induce liver inflammation, which might contribute to outgrowth of liver metastases.

AB - Most patients with pancreatic ductal adenocarcinoma (PDAC) undergoing curative resection relapse within months, often with liver metastases. The hepatic microenvironment determines induction and reversal of dormancy during metastasis. Both tumor growth and metastasis depend on the Tumor necrosis factor (TNF)-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2). This study investigated the interplay of TRAIL-R2 and the hepatic microenvironment in liver metastases formation and the impact of surgical resection. Although TRAIL-R2-knockdown (PancTu-I shTR2) decreased local relapses and number of macroscopic liver metastases after primary tumor resection in an orthotopic PDAC model, the number of micrometastases was increased. Moreover, abdominal surgery induced liver inflammation involving activation of hepatic stellate cells (HSCs) into hepatic myofibroblasts (HMFs). In coculture with HSCs, proliferation of PancTu-I shTR2 cells was significantly lower compared to PancTu-I shCtrl cells, an effect still observed after switching coculture from HSC to HMF, mimicking surgery-mediated liver inflammation and enhancing cell proliferation. CXCL-8/IL-8 blockade diminished HSC-mediated growth inhibition in PancTu-I shTR2 cells, while Vascular Endothelial Growth Factor (VEGF) neutralization decreased HMF-mediated proliferation. Overall, this study points to an important role of TRAIL-R2 in PDAC cells in the interplay with the hepatic microenvironment during metastasis. Resection of primary PDAC seems to induce liver inflammation, which might contribute to outgrowth of liver metastases.

KW - Journal Article

U2 - 10.3390/cancers11060745

DO - 10.3390/cancers11060745

M3 - SCORING: Journal article

C2 - 31146405

VL - 11

JO - CANCERS

JF - CANCERS

SN - 2072-6694

IS - 6

ER -