1. ¹Department of Surgery, Technische Universität München, Munich, Germany
2. ²Department of Surgery, University of Heidelberg, Heidelberg, Germany
3. ³Institute of Pathology, Technische Universität München, Munich, Germany
4. ⁴Institute of Pathology, Helmholtz Zentrum München, Neuherberg, Germany
5. ⁵Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
6. ⁶Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
7. ⁷Department of Medical Biochemistry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, and CREST of JST, Japan
8. ⁸Department of Physiology, United Arab Emirates University, Faculty of Medicine and Health Sciences, Al Ain, UAE

Correspondence: Dr R Hennig, Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Ismaninger St. 22, 81675 Munich, Germany. E-mail: rene.hennig@chir.med.tu-muenchen.de

⁹These authors contributed equally to this work.

Revised 12 August 2008; Accepted 14 August 2008; Published online 9 September 2008.

Abstract

Pancreatic cancer has an abysmal prognosis. Targets for early detection, prevention and therapy are desperately needed. Inflammatory pathways have an important impact on tumour growth and progression. Expression of BLT2 (the second leukotriene B₄ receptor) was investigated by real-time RT–PCR and immunohistochemistry. Cell proliferation was studied after stable transfection with BLT2, after treatment with siRNA and Compound A as an agonist. BLT2 is expressed in all pancreatic cancer cell lines. Results from real-time RT–PCR revealed significant overexpression of BLT2 in malignant intraductal papillary mucinous neoplasias (IPMNs) and pancreatic adenocarcinoma. Intense staining was evident in IPMNs, infiltrating tumour cells and advanced pancreatic intraepithelial neoplasias (PanINs) but not in normal ductal cells. Overexpression of BLT2 as well as stimulation of Colo357, Panc-1 and AsPC1 cells with Compound A caused a significant increase in tumour cell proliferation, an effect reversed after siRNA treatment. This study demonstrates for the first time the expression of BLT2 in the pancreas and overexpression in pancreatic cancers and malignant IPMNs in particular. Upregulation of BLT2 is already evident in precursor lesions (PanINs, IPMNs). Overexpression of this receptor leads to significant growth stimulation. Therefore, we suggest BLT2 as a new target for chemoprevention and therapy for pancreatic cancer.