The role of the antileukoprotease SLPI in smoking‐induced human papillomavirus‐independent head and neck squamous cell carcinomas. Issue 6 (23rd September 2013)

• Record Type: Journal Article
• Authors: Quabius, Elgar Susanne; Möller, Paul; Haag, Jochen; Pfannenschmidt, Saskia; Hedderich, Jürgen; Görögh, Tibor; Röcken, Christoph; Hoffmann, Markus
• Is Part Of: International journal of cancer. Volume 134:Issue 6(2014:Mar. 15)
• Page Start: 1323
• Page End: 1334
• Publication Date: 2013-09-23
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.28462
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Recently, we showed that increased SLPI levels prevent human papillomavirus (HPV) infections and metastasis in smoking‐induced, non‐HPV‐driven head and neck squamous cell carcinoma (HNSCC). Here, we focus on the role of SLPI in non‐HPV‐driven HNSCC, investigating tumor tissue and non‐neoplastic mucosa from the same patients and from non‐HNSCC patients. Gene and protein expression of <italic>SLPI</italic> and gene expression of <italic>annexin 2</italic> (a SLPI receptor), nicotine receptor (<italic>α7AChR</italic>) and arylhydrocarbon receptor (<italic>AhR</italic>) were analyzed in HNSCC patients (20 smokers; 16 nonsmokers). SLPI‐results were correlated with the patients' HPV status. Non‐neoplastic mucosa of HNSCC patients and normal mucosa from non‐HNSCC individuals (18 smokers; 20 nonsmokers) was analyzed for the same parameters. Tissue of the inferior turbinate (<italic>n</italic> = 10) was incubated with nicotine for analysis of the same genes. <italic>SLPI</italic> gene expression in tumor tissue was 109.26 ± 23.08 times higher in smokers versus nonsmokers. Non‐neoplastic mucosa of smokers showed also higher <italic>SLPI</italic> gene expression (10.49 ± 1.89‐fold non‐HNSCC; 18.02 ± 3.93‐fold HNSCC patients). <italic>Annexin 2</italic> gene expression was also increased in smokers. SLPI data were corroborated by immunohistochemistry. A nicotine dependent correlation between <italic>SLPI</italic> and <italic>annexin 2</italic> gene expression (<italic>r</italic><sup>2</sup> = 0.15, <italic>p</italic> < 0.001) was shown <italic>ex vivo</italic>. Nicotine and smoking increased α7AChR and AhR gene expression. Five patients, showing no/low SLPI expression, were HPV16‐positive. A significant correlation between smoking and SLPI expression in tumors and to our knowledge for the first time in mucosa of HNSCC and non‐HNSCC patients was established. Together with the finding that all patients with HPV infection showed no/low SLPI expression, these data support our intriguing hypothesis that smoking induced upregulated SLPI prevents HPV infections.</p> </abstract>