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

Molecular Cancer

Research

Zheng Pan¹  Tamar Samkharadze¹  Mert Erkan¹  Helmut Friess¹  Xiaohua Jiang¹  Jörg Kleeff²  Nathalia A. Giese³  Christian Schwager⁴  Ute Wirkner⁴  Jürgen Debus⁴  Nadine Weis⁴  Wilhelm Ansorge⁴  Peter E. Huber⁴  Amir Abdollahi⁵ 

[1] Department of General Surgery, Technische Universität München, Munich, Germany;Department of General Surgery, Technische Universität München, Munich, Germany;Center of Cancer Systems Biology, Dept. of Medicine, Caritas St. Elizabeth's Medical Center, Tufts University School of Medicine, 02135-2997, Boston, Massachusetts, USA;Department of General Surgery, University of Heidelberg, Heidelberg, Germany;Department of Radiation Oncology, German Cancer Research Center (DKFZ) and University of Heidelberg, Heidelberg, Germany;Department of Radiation Oncology, German Cancer Research Center (DKFZ) and University of Heidelberg, Heidelberg, Germany;Center of Cancer Systems Biology, Dept. of Medicine, Caritas St. Elizabeth's Medical Center, Tufts University School of Medicine, 02135-2997, Boston, Massachusetts, USA;Children's Hospital Boston, Vascular Biology Program & Harvard Medical School, Department of Surgery, Karp Family Research Laboratories, 02115, Boston, Massachusetts, USA;

关键词: Chronic Pancreatitis;    Pancreatic Cancer Cell;    Stellate Cell;    Hepatic Stellate Cell;    Pancreatic Ductal Adenocarcinoma;   

DOI  :  10.1186/1476-4598-9-88

 received in 2009-09-14, accepted in 2010-04-23,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundTissue 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.MethodsStellate 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.ResultsExpression 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.ConclusionsWe 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.

【 授权许可】

Unknown   
© Erkan et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.