Expression of a prometastatic splice variant of osteopontin, OPNC, in human pancreatic ductal adenocarcinoma
| Autor: | Georg F. Weber, Jennifer Sullivan, Charles J. Yeo, Laurel Blair, David T. Denhardt, Amer Alnajar, Chee Yuan Ng, Qiaoke Gong, Hwyda A. Arafat, Galina Chipitsyna, Tamer Aziz, Agnieszka K. Witkiewicz |
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| Rok vydání: | 2009 |
| Předmět: |
Pathology
medicine.medical_specialty Nicotine Pancreatic disease education Article stomatognathic system Cell Line Tumor Gene expression medicine Ultraviolet light Tumor Cells Cultured Humans Protein Isoforms Osteopontin RNA Messenger biology business.industry Smoking Cancer medicine.disease Immunohistochemistry Pancreatic Neoplasms Computers Handheld Cancer cell biology.protein Surgery business medicine.drug Carcinoma Pancreatic Ductal |
| Zdroj: | Surgery. 146(2) |
| ISSN: | 1532-7361 |
| Popis: | 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. Conclusion 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. |
| Databáze: | OpenAIRE |
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