1. ¹Centre for Molecular Oncology, Institute of Cancer and the CR-UK Clinical Centre, Barts and The London, Charterhouse Square, London, UK
2. ²Centre for Tumour Biology, Institute of Cancer and the CR-UK Clinical Centre, Barts and The London, Charterhouse Square, London, UK
3. ³Department of Medicine/Division of Hematology-Oncology, UCLA David Geffen School of Medicine Los Angeles, Los Angeles, CA, USA
4. ⁴Clinic for General Surgery and Thoracic Surgery, University of Kiel, Kiel, Germany

Correspondence: Professor NR Lemoine, Centre for Molecular Oncology, Institute of Cancer, Barts and The London School of Medicine and Dentistry, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK. E-mail: nick.lemoine@cancer.org.uk

Received 3 April 2006; Revised 12 July 2006; Accepted 16 August 2006; Published online 9 October 2006.

Abstract

Pancreatic ductal adenocarcinoma is a devastating disease, characterized by a rapid progression and poor treatment response. Using gene expression profiling of pancreatic cancer tissues, we previously identified periostin as a potential diagnostic and therapeutic target. In this study, we report the overexpression of periostin in a larger set of pancreatic cancer tissues and show that although the periostin transcript is exclusively expressed in tumour cells, the protein product is only detected in the extracellular matrix adjacent to cancer cells. Using an enzyme-linked immunosorbent assay (ELISA) assay, we show significantly increased levels of periostin in the sera of pancreatic cancer patients compared to non-cancer controls. We demonstrate that periostin promotes the invasiveness of tumour cells by increasing the motility of cells without inducing expression of proteases, and enhances the survival of tumour cells exposed to hypoxic conditions. At the molecular level, we provide evidence that the ₆₄ integrin complex acts as the cell receptor of periostin in pancreatic cancer cells and that interaction promotes phosphorylation of focal adhesion kinase (FAK) and protein kinase B (AKT) though activation of the PI3 kinase pathway, but not the RAS/MEK/ERK pathway. These findings suggest an important role of periostin in pancreatic cancer and provide a rationale to study periostin for diagnostic and therapeutic applications.