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01-08-2009 | Translational Research and Biomarkers

Involvement of CD40 Targeting miR-224 and miR-486 on the Progression of Pancreatic Ductal Adenocarcinomas

Authors: Soeren Torge Mees, MD, Wolf Arif Mardin, MD, Sonja Sielker, Edith Willscher, Norbert Senninger, PhD, Christina Schleicher, MD, Mario Colombo-Benkmann, PhD, Joerg Haier, PhD

Published in: Annals of Surgical Oncology | Issue 8/2009

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.

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Title: Involvement of CD40 Targeting miR-224 and miR-486 on the Progression of Pancreatic Ductal Adenocarcinomas
Authors: Soeren Torge Mees, MD
Wolf Arif Mardin, MD
Sonja Sielker
Edith Willscher
Norbert Senninger, PhD
Christina Schleicher, MD
Mario Colombo-Benkmann, PhD
Joerg Haier, PhD
Publication date: 01-08-2009
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 8/2009
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-009-0531-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Involvement of CD40 Targeting miR-224 and miR-486 on the Progression of Pancreatic Ductal Adenocarcinomas

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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