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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.

SUBMITTER: Pilarsky C

PROVIDER: S-EPMC3828895 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

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Activation of Wnt signalling in stroma from pancreatic cancer identified by gene expression profiling.

Pilarsky Christian C Ammerpohl Ole O Sipos Bence B Dahl Edgar E Hartmann Arndt A Wellmann Axel A Braunschweig Till T Löhr Matthias M Jesenofsky Ralf R Friess Helmut H Wente Moritz Nicolas MN Kristiansen Glen G Jahnke Beatrix B Denz Axel A Rückert Felix F Schackert Hans K HK Klöppel Günter G Kalthoff Holger H Saeger Hans Detlev HD Grützmann Robert R

Journal of cellular and molecular medicine 20080224 6B

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 pancre ...[more]

PMID: 18298655

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Activation of Wnt signalling in stroma from pancreatic cancer identified by gene expression profiling.

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Activation of Wnt signalling in stroma from pancreatic cancer identified by gene expression profiling.

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