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Involvement of CD40 targeting miR-224 and miR-486 on the progression of pancreatic ductal adenocarcinomas

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Involvement of CD40 targeting miR-224 and miR-486 on the progression of pancreatic ductal adenocarcinomas. / Mees, Soeren Torge; Mardin, Wolf Arif; Sielker, Sonja; Willscher, Edith; Senninger, Norbert; Schleicher, Christina; Colombo-Benkmann, Mario; Haier, Joerg.

in: ANN SURG ONCOL, Jahrgang 16, Nr. 8, 08.2009, S. 2339-50.

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

Harvard

Mees, ST, Mardin, WA, Sielker, S, Willscher, E, Senninger, N, Schleicher, C, Colombo-Benkmann, M & Haier, J 2009, 'Involvement of CD40 targeting miR-224 and miR-486 on the progression of pancreatic ductal adenocarcinomas', ANN SURG ONCOL, Jg. 16, Nr. 8, S. 2339-50. https://doi.org/10.1245/s10434-009-0531-4

APA

Mees, S. T., Mardin, W. A., Sielker, S., Willscher, E., Senninger, N., Schleicher, C., Colombo-Benkmann, M., & Haier, J. (2009). Involvement of CD40 targeting miR-224 and miR-486 on the progression of pancreatic ductal adenocarcinomas. ANN SURG ONCOL, 16(8), 2339-50. https://doi.org/10.1245/s10434-009-0531-4

Vancouver

Mees ST, Mardin WA, Sielker S, Willscher E, Senninger N, Schleicher C et al. Involvement of CD40 targeting miR-224 and miR-486 on the progression of pancreatic ductal adenocarcinomas. ANN SURG ONCOL. 2009 Aug;16(8):2339-50. https://doi.org/10.1245/s10434-009-0531-4

Bibtex

@article{d6b6ae2d8bd8469bb24d3e62d518f478,
title = "Involvement of CD40 targeting miR-224 and miR-486 on the progression of pancreatic ductal adenocarcinomas",
abstract = "BACKGROUND: Genetic and epigenetic alterations during development of pancreatic ductal adenocarcinomas (PDAC) are well known. Genetic and epigenetic data were correlated with tumor biology to find specific alterations responsible for invasion and metastasis in pancreatic ductal adenocarcinomas.METHODS: A total of 16 human PDAC cell lines were used in murine orthotopic PDAC models. By means of standardized dissemination scores, local invasion and metastatic spread were assessed. mRNA and microRNA expression were studied by microarray and TaqMan low-density array. Quantitative real-time-polymerase chain reaction and flow cytometry were used for expression validation.RESULTS: CD40 was detected as a relevant target gene for differentially expressed miRNAs observed in highly invasive and metastatic PDAC only. A significant overexpression (P < .05) of CD40-related miRNAs miR-224 and miR-486 was detected in highly invasive and metastatic PDAC, whereas CD40 mRNA expression was not significantly altered. Instead, CD40 protein expression at cell surfaces of these highly invasive and metastatic PDAC was significantly reduced (P < .01).CONCLUSIONS: Epigenetic alterations with upregulated CD40-targeting miR-224 and miR-486 are related to downregulated CD40 protein expression at cell surfaces in highly invasive and metastatic PDAC. Thus, miRNA-regulated CD40 expression seems to play an important role in progression of PDAC. These data suggest a diagnostic and therapeutic potential for CD40 and/or its targeting miRNAs in PDAC.",
keywords = "Adenocarcinoma, Animals, Antigens, CD40, Carcinoma, Pancreatic Ductal, Disease Progression, Flow Cytometry, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Male, Mice, Mice, Nude, MicroRNAs, Oligonucleotide Array Sequence Analysis, Pancreatic Neoplasms, RNA, Messenger, Tumor Cells, Cultured, Xenograft Model Antitumor Assays",
author = "Mees, {Soeren Torge} and Mardin, {Wolf Arif} and Sonja Sielker and Edith Willscher and Norbert Senninger and Christina Schleicher and Mario Colombo-Benkmann and Joerg Haier",
year = "2009",
month = aug,
doi = "10.1245/s10434-009-0531-4",
language = "English",
volume = "16",
pages = "2339--50",
journal = "ANN SURG ONCOL",
issn = "1068-9265",
publisher = "Springer New York",
number = "8",

}

RIS

TY - JOUR

T1 - Involvement of CD40 targeting miR-224 and miR-486 on the progression of pancreatic ductal adenocarcinomas

AU - Mees, Soeren Torge

AU - Mardin, Wolf Arif

AU - Sielker, Sonja

AU - Willscher, Edith

AU - Senninger, Norbert

AU - Schleicher, Christina

AU - Colombo-Benkmann, Mario

AU - Haier, Joerg

PY - 2009/8

Y1 - 2009/8

N2 - BACKGROUND: Genetic and epigenetic alterations during development of pancreatic ductal adenocarcinomas (PDAC) are well known. Genetic and epigenetic data were correlated with tumor biology to find specific alterations responsible for invasion and metastasis in pancreatic ductal adenocarcinomas.METHODS: A total of 16 human PDAC cell lines were used in murine orthotopic PDAC models. By means of standardized dissemination scores, local invasion and metastatic spread were assessed. mRNA and microRNA expression were studied by microarray and TaqMan low-density array. Quantitative real-time-polymerase chain reaction and flow cytometry were used for expression validation.RESULTS: CD40 was detected as a relevant target gene for differentially expressed miRNAs observed in highly invasive and metastatic PDAC only. A significant overexpression (P < .05) of CD40-related miRNAs miR-224 and miR-486 was detected in highly invasive and metastatic PDAC, whereas CD40 mRNA expression was not significantly altered. Instead, CD40 protein expression at cell surfaces of these highly invasive and metastatic PDAC was significantly reduced (P < .01).CONCLUSIONS: Epigenetic alterations with upregulated CD40-targeting miR-224 and miR-486 are related to downregulated CD40 protein expression at cell surfaces in highly invasive and metastatic PDAC. Thus, miRNA-regulated CD40 expression seems to play an important role in progression of PDAC. These data suggest a diagnostic and therapeutic potential for CD40 and/or its targeting miRNAs in PDAC.

AB - BACKGROUND: Genetic and epigenetic alterations during development of pancreatic ductal adenocarcinomas (PDAC) are well known. Genetic and epigenetic data were correlated with tumor biology to find specific alterations responsible for invasion and metastasis in pancreatic ductal adenocarcinomas.METHODS: A total of 16 human PDAC cell lines were used in murine orthotopic PDAC models. By means of standardized dissemination scores, local invasion and metastatic spread were assessed. mRNA and microRNA expression were studied by microarray and TaqMan low-density array. Quantitative real-time-polymerase chain reaction and flow cytometry were used for expression validation.RESULTS: CD40 was detected as a relevant target gene for differentially expressed miRNAs observed in highly invasive and metastatic PDAC only. A significant overexpression (P < .05) of CD40-related miRNAs miR-224 and miR-486 was detected in highly invasive and metastatic PDAC, whereas CD40 mRNA expression was not significantly altered. Instead, CD40 protein expression at cell surfaces of these highly invasive and metastatic PDAC was significantly reduced (P < .01).CONCLUSIONS: Epigenetic alterations with upregulated CD40-targeting miR-224 and miR-486 are related to downregulated CD40 protein expression at cell surfaces in highly invasive and metastatic PDAC. Thus, miRNA-regulated CD40 expression seems to play an important role in progression of PDAC. These data suggest a diagnostic and therapeutic potential for CD40 and/or its targeting miRNAs in PDAC.

KW - Adenocarcinoma

KW - Animals

KW - Antigens, CD40

KW - Carcinoma, Pancreatic Ductal

KW - Disease Progression

KW - Flow Cytometry

KW - Gene Expression Profiling

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Male

KW - Mice

KW - Mice, Nude

KW - MicroRNAs

KW - Oligonucleotide Array Sequence Analysis

KW - Pancreatic Neoplasms

KW - RNA, Messenger

KW - Tumor Cells, Cultured

KW - Xenograft Model Antitumor Assays

U2 - 10.1245/s10434-009-0531-4

DO - 10.1245/s10434-009-0531-4

M3 - SCORING: Journal article

C2 - 19475450

VL - 16

SP - 2339

EP - 2350

JO - ANN SURG ONCOL

JF - ANN SURG ONCOL

SN - 1068-9265

IS - 8

ER -