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

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.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.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.Emerging body of data suggest a critical role for stellate cells in the pathophysiology of pancreatic cancer and chronic inflammatory diseases [1-5]. Hepatic stellate cells (HSC) were first described by Karl von Kupffer in 1876, however similar cells in the pancreas were first observed in 1980s [1,3,6]. In 1998 Bachem and Apte isolated and cultured pancreatic stellate cells (PSC) [7,8]. Morphologic, functional and gene expression studies revealed that PSC resemble HSC characteristics and therefore may possibly share a common origin [3,9]. However, the origin of stellate cells is still controversially debated. Mesenchymal [