BLT2 is expressed in PanINs, IPMNs, pancreatic cancer and stimulates tumour cell proliferation

R. Hennig*, T. Osman, I. Esposito, N. Giese, S. M. Rao, X. Z. Ding, W. G. Tong, M. W. Büchler, T. Yokomizo, H. Friess, T. E. Adrian

*Corresponding author for this work

Research output: Contribution to journalArticle

46 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1064-1073
Number of pages10
JournalBritish Journal of Cancer
Volume99
Issue number7
DOIs
StatePublished - Oct 7 2008

Keywords

  • BLT2
  • IPMN
  • Leukotriene B
  • PanIN
  • Pancreatic cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Hennig, R., Osman, T., Esposito, I., Giese, N., Rao, S. M., Ding, X. Z., Tong, W. G., Büchler, M. W., Yokomizo, T., Friess, H., & Adrian, T. E. (2008). BLT2 is expressed in PanINs, IPMNs, pancreatic cancer and stimulates tumour cell proliferation. British Journal of Cancer, 99(7), 1064-1073. https://doi.org/10.1038/sj.bjc.6604655