Expression of a prometastatic splice variant of osteopontin, OPNC, in human pancreatic ductal adenocarcinoma.
BACKGROUND
Osteopontin (OPN) is a secreted phosphoprotein that confers on cancer cells a migratory phenotype. We demonstrated recently that nicotine, a major risk factor in pancreatic ductal adenocarcinoma (PDA), increases OPN expression in PDA cells. An OPN splice variant, OPNc, supports anchorage independence and maybe the most potent OPN isoform to convey metastatic behavior. In this study, we tested the effect of nicotine on OPNc expression and analyzed the correlation between total OPN/OPNc levels and patients' smoking history.


METHODS
Real-time polymerase chain reaction and ultraviolet light illumination of ethidium-bromide staining were used to examine the mRNA expression in tissue and in PDA cells treated with or without nicotine (3-300 nmol/L). OPN and OPNc were localized by immunohistochemistry, and an enzyme-linked immunosorbent assay was used to analyze OPN serum levels.


RESULTS
Nicotine treatment of PDA cells selectively induced de novo expression of OPNc. OPNc was found in 87% of invasive PDA lesions, of which 73% were found in smokers. The levels of OPNc correlated well with higher expression levels of total OPN in the tissue and serum from patients with invasive PDA.


CONCLUSIONS
Our data suggest that smoking and nicotine may contribute to PDA metastatic potential through promoting OPNc expression. Although the direct role of OPNc in PDA progression is not defined, OPNc may have value as a diagnostic and prognostic marker, especially in invasive PDA.
Sullivan
Jennifer
J
Department of Surgery, Jefferson Pancreatic, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Blair
Laurel
L
Alnajar
Amer
A
Aziz
Tamer
T
Ng
Chee Yuan
CY
Chipitsyna
Galina
G
Gong
Qiaoke
Q
Witkiewicz
Agnes
A
Weber
Georg F
GF
Denhardt
David T
DT
Yeo
Charles J
CJ
Arafat
Hwyda A
HA
D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000556:secondary*; D045744:Cell Line, Tumor; D034201:Computers, Handheld; D006801:Humans; D007150:Immunohistochemistry; D009538:Nicotine / Q000494:pharmacology; D053495:Osteopontin / Q000235:genetics* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012907:Smoking; D014407:Tumor Cells, Cultured
D020033:Protein Isoforms; D012333:RNA, Messenger; D053495:Osteopontin; D009538:Nicotine