title: Activation of Wnt signalling in stroma from pancreatic cancer identified by gene expression profiling.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is characterized by an abundant desmoplastic stroma. Interactions between cancer and stromal cells play a critical role in tumour invasion, metastasis and chemoresistance. Therefore, we hypothesized that gene expression profile of the stromal components of pancreatic carcinoma is different from chronic pancreatitis and reflects the interaction with the tumour. We investigated the gene expression of eleven stromal tissues from PDAC, nine from chronic pancreatitis and cell lines of stromal origin using the Affymetrix U133 GeneChip set. The tissue samples were microdissected, the RNA was extracted, amplified and labelled using a repetitive in vitro transcription protocol. Differentially expressed genes were identified and validated using quantitative RT-PCR and immuno-histochemistry. We found 255 genes to be overexpressed and 61 genes to be underexpressed within the stroma of pancreatic carcinoma compared to the stroma of chronic pancreatitis. Analysis of the involved signal transduction pathways revealed a number of genes associated with the Wnt pathway of which the differential expression of SFRP1 and WNT5a was confirmed using immunohistochemistry. Moreover, we could demonstrate that WNT5a expression was induced in fibroblasts during cocultivation with a pancreatic carcinoma cell line. The identified differences in the expression profile of stroma cells derived from tumour compared to cells of inflammatory origin suggest a specific response of the tissue surrounding malignant cells. The overexpression of WNT5a, a gene involved in the non canonical Wnt signalling and chondrocyte development might contribute to the strong desmoplastic reaction seen in pancreatic cancer.
authors.affiliation: Department of Visceral-, Thoracic- and Vascular Surgery, University Hospital Carl Gustav Carus, Technical University of Dresden, Dresden, Germany. christian.pilarsky@mailbox.tu-dresden.de
authors.forename: Christian
authors.initials: C
authors.lastname: Pilarsky
authors.forename: Ole
authors.initials: O
authors.lastname: Ammerpohl
authors.forename: Bence
authors.initials: B
authors.lastname: Sipos
authors.forename: Edgar
authors.initials: E
authors.lastname: Dahl
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.forename: Axel
authors.initials: A
authors.lastname: Wellmann
authors.forename: Till
authors.initials: T
authors.lastname: Braunschweig
authors.forename: Matthias
authors.initials: M
authors.lastname: Löhr
authors.forename: Ralf
authors.initials: R
authors.lastname: Jesenofsky
authors.forename: Ralf
authors.initials: R
authors.lastname: Jesnowski
authors.forename: Helmut
authors.initials: H
authors.lastname: Friess
authors.forename: Moritz Nicolas
authors.initials: MN
authors.lastname: Wente
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.forename: Beatrix
authors.initials: B
authors.lastname: Jahnke
authors.forename: Axel
authors.initials: A
authors.lastname: Denz
authors.forename: Felix
authors.initials: F
authors.lastname: Rückert
authors.forename: Hans K
authors.initials: HK
authors.lastname: Schackert
authors.forename: Günter
authors.initials: G
authors.lastname: Klöppel
authors.forename: Holger
authors.initials: H
authors.lastname: Kalthoff
authors.forename: Hans Detlev
authors.initials: HD
authors.lastname: Saeger
authors.forename: Robert
authors.initials: R
authors.lastname: Grützmann
mesh_terms: D045744:Cell Line, Tumor; D016000:Cluster Analysis; D018920:Coculture Techniques; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006801:Humans; D007150:Immunohistochemistry; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000235:genetics*; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology*; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D051153:Wnt Proteins