Expression and regulation of nicotine receptor and osteopontin isoforms in human pancreatic ductal adenocarcinoma.

Authors

• Jennifer Sullivan
• Laurel Blair
• Amer Alnajar
• Tamer Aziz
• Galina Chipitsyna
• Qiaoke Gong
• Charles J Yeo
• Hwyda A Arafat

Publication/Presentation Date

7-1-2011

Abstract

Osteopontin (OPN) is a secreted phospho-protein that confers on cancer cells a migratory phenotype. We have recently shown that nicotine, a risk factor in pancreatic ductal adenocarcinoma (PDA), induces an alpha7-nicotine acetylcholine receptor (α7-nAChR)-mediated increase of OPN in PDA cells. In this study, we tested nicotine's effect on the expression of OPN splice variants (OPNa, b, c) in PDA cells. We also analyzed the correlation between patients' smoking history with OPN and α7-nAChR levels. RT-PCR and UV-light-illumination of ethidium-bromide staining were used to examine the mRNA expression in tissue and PDA cells treated with or without nicotine (3-300 nM). Localization of total OPN, OPNc and α7-nAChR was analyzed by immunohistochemistry, and their mRNA tissue expression levels were correlated with the patients' smoking history. PDA cells expressed varying levels of OPNa, OPNb, and α7-nAChR. Nicotine treatment selectively induced denovo expression of OPNc and increased α7-nAChR expression levels. In PDA tissue, OPNc was found in 87% of lesions, of which 73% were smokers. OPNc and total OPN levels were correlated in the tissue from patients with invasive PDA. Nicotine receptor was expressed in the invasive and premalignant lesions without clear correlation with smoking history. We show here for the first time that α7-nAChR is expressed in PDA cells and tissues and is regulated by nicotine in PDA cells. This, together with our previous findings that α7-nAChR mediates the metastatic effects of nicotine in PDA, suggest that combined targeting of α7-nAChR and OPNc could be a valid novel therapeutic strategy for invasive PDA, especially in the smoking population.

Volume

26

Issue

7

First Page

893

Last Page

904

ISSN

1699-5848

Published In/Presented At

Sullivan, J., Blair, L., Alnajar, A., Aziz, T., Chipitsyna, G., Gong, Q., Yeo, C. J., & Arafat, H. A. (2011). Expression and regulation of nicotine receptor and osteopontin isoforms in human pancreatic ductal adenocarcinoma. Histology and histopathology, 26(7), 893–904. https://doi.org/10.14670/HH-26.893

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

21630219

Department(s)

Administration and Leadership

Document Type

Article