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Molecular Cancer
Published in: Molecular Cancer 1/2010

Open Access 01-12-2010 | Research

Organ-, inflammation- and cancer specific transcriptional fingerprints of pancreatic and hepatic stellate cells

Authors: Mert Erkan, Nadine Weis, Zheng Pan, Christian Schwager, Tamar Samkharadze, Xiaohua Jiang, Ute Wirkner, Nathalia A. Giese, Wilhelm Ansorge, Jürgen Debus, Peter E. Huber, Helmut Friess, Amir Abdollahi, Jörg Kleeff

Published in: Molecular Cancer | Issue 1/2010

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Abstract

Background

Tissue fibrosis is an integral component of chronic inflammatory (liver and pancreas) diseases and pancreatic cancer. Activated pancreatic- (PSC) and hepatic- (HSC) stellate cells play a key role in fibrogenesis. To identify organ- and disease-specific stellate cell transcriptional fingerprints, we employed genome-wide transcriptional analysis of primary human PSC and HSC isolated from patients with chronic inflammation or cancer.

Methods

Stellate cells were isolated from patients with pancreatic ductal adenocarcinoma (n = 5), chronic pancreatitis (n = 6), liver cirrhosis (n = 5) and liver metastasis of pancreatic ductal adenocarcinoma (n = 6). Genome-wide transcriptional profiles of stellate cells were generated using our 51K human cDNA microarray platform. The identified organ- and disease specific genes were validated by quantitative RT-PCR, immunoblot, ELISA, immunocytochemistry and immunohistochemistry.

Results

Expression profiling identified 160 organ- and 89 disease- specific stellate cell transcripts. Collagen type 11a1 (COL11A1) was discovered as a novel PSC specific marker with up to 65-fold higher expression levels in PSC compared to HSC (p < 0.0001). Likewise, the expression of the cytokine CCL2 and the cell adhesion molecule VCAM1 were confined to HSC. PBX1 expression levels tend to be increased in inflammatory- vs. tumor- stellate cells. Intriguingly, tyrosine kinase JAK2 and a member of cell contact-mediated communication CELSR3 were found to be selectively up-regulated in tumor stellate cells.

Conclusions

We identified and validated HSC and PSC specific markers. Moreover, novel target genes of tumor- and inflammation associated stellate cells were discovered. Our data may be instrumental in developing new tailored organ- or disease-specific targeted therapies and stellate cell biomarkers.
Appendix
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Metadata
Title
Organ-, inflammation- and cancer specific transcriptional fingerprints of pancreatic and hepatic stellate cells
Authors
Mert Erkan
Nadine Weis
Zheng Pan
Christian Schwager
Tamar Samkharadze
Xiaohua Jiang
Ute Wirkner
Nathalia A. Giese
Wilhelm Ansorge
Jürgen Debus
Peter E. Huber
Helmut Friess
Amir Abdollahi
Jörg Kleeff
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2010
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-9-88

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