Human α-defensin (DEFA) gene expression helps to characterise benign and malignant salivary gland tumours

BMC Cancer

Matthias Wenghoefer³  Natalija Novak⁴  Jean-Pierre Allam⁴  Hans-Peter Fischer⁵  Soeren Jepsen⁶  Rudolf Reich³  Jan Reckenbeil³  Dominik Kraus¹  Annette Pantelis²  Jochen Winter⁶ 

[1]Department of Prosthodontics, Preclinical Education, and Material Science, University of Bonn, Welschnonnenstr, 1753111, Bonn, Germany

[2]Waldkrankenhaus, Waldstrasse 73, 53177, Bonn, Germany

[3]Department of Oral & Maxillofacial Plastic Surgery, University of Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany

[4]Department of Dermatology and Allergy, University of Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany

[5]Department of Pathology, University of Bonn, Bonn, Germany

[6]Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Welschnonnenstr, 1753111, Bonn, Germany

关键词: Defensins;    Tumour;    Salivary gland;    DEFA 4;    DEFA 1/3;   

Others  :  1080144
DOI  :  10.1186/1471-2407-12-465

 received in 2012-05-08, accepted in 2012-10-02,  发布年份 2012

【 摘 要 】

Background

Because of the infrequence of salivary gland tumours and their complex histopathological diagnosis it is still difficult to exactly predict their clinical course by means of recurrence, malignant progression and metastasis. In order to define new proliferation associated genes, purpose of this study was to investigate the expression of human α-defensins (DEFA) 1/3 and 4 in different tumour entities of the salivary glands with respect to malignancy.

Methods

Tissue of salivary glands (n=10), pleomorphic adenomas (n=10), cystadenolymphomas (n=10), adenocarcinomas (n=10), adenoidcystic carcinomas (n=10), and mucoepidermoid carcinomas (n=10) was obtained during routine surgical procedures. RNA was extracted according to standard protocols. Transcript levels of DEFA 1/3 and 4 were analyzed by quantitative realtime PCR and compared with healthy salivary gland tissue. Additionally, the proteins encoded by DEFA 1/3 and DEFA 4 were visualized in paraffin-embedded tissue sections by immunohistochemical staining.

Results

Human α-defensins are traceable in healthy as well as in pathological altered salivary gland tissue. In comparison with healthy tissue, the gene expression of DEFA 1/3 and 4 was significantly (p<0.05) increased in all tumours – except for a significant decrease of DEFA 4 gene expression in pleomorphic adenomas and a similar transcript level for DEFA 1/3 compared to healthy salivary glands.

Conclusions

A decreased gene expression of DEFA 1/3 and 4 might protect pleomorphic adenomas from malignant transformation into adenocarcinomas. A similar expression pattern of DEFA-1/3 and -4 in cystadenolymphomas and inflamed salivary glands underlines a potential importance of immunological reactions during the formation of Warthin’s tumour.

【 授权许可】

   
2012 Winter et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Machtens E: Speicheldrüsenerkrankungen. Mund Kiefer Gesichts Chir 2000, 4:401-413.
• [2]Röser K, Jakel KT, Herbst H, Loning T: Immunohistochemical characterization of salivary gland tumors with tissue micro-arrays. Pathologe 2005, 26(5):345-352.
• [3]Jaehne M, Roeser K, Jaekel T, Schepers JD, Albert N, Loning T: Clinical and immunohistologic typing of salivary duct carcinoma: a report of 50 cases. Cancer 2005, 103(12):2526-2533.
• [4]Pantelis A, Wenghoefer M, Haas S, Merkelbach-Bruse S, Pantelis D, Jepsen S, Bootz F, Winter J: Down regulation and nuclear localization of human beta-defensin-1 in pleomorphic adenomas of salivary glands. Oral Oncol 2009, 45(6):526-530.
• [5]Wenghoefer M, Pantelis A, Dommisch H, Götz W, Reich R, Bergé S, Martini M, Allam JP, Jepsen S, Merkelbach-Bruse S, Fischer HP, Novak N, Winter J: Nuclear hBD-1 accumulation in malignant salivary gland tumors. BMC Cancer 2008, 8:290. BioMed Central Full Text
• [6]Winter J, Mohr S, Pantelis A, Kraus D, Allam JP, Novak N, Reich R, Martini M, Jepsen S, Götz W, Wenghoefer M: IGF-1 deficiency in combination with a low basic hBD-2 and hBD-3 gene expression might counteract malignant transformation in pleomorphic adenomas in vitro. Cancer Invest 2011, 30(2):106-113.
• [7]Ganz T: Defensins: antimicrobial peptides of innate immunity. Nature Rev. Immunol. 2003, 3:710-720.
• [8]Lehrer RI: Primate defensins. Nature Rev. Microbiol. 2004, 2:727-738.
• [9]Brogden KA: Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nature Rev. Microbiol. 2005, 3:238-250.
• [10]Hazlett L, Wu M: Defensins in innate immunity. Cell Tissue Res 2011, 343:175-188.
• [11]Winter J, Wenghoefer M: Review: Human Defensins: Potential Tools for Clinical Applications. Polymers 2012, 4(1):691-709.
• [12]Mathews M, Jia HP, Guthmiller JM, Losh G, Graham S, Johnson GK, Tack BF, McCray PB: Production of β-defensin antimicrobial peptides by the oral mucosa and salivary glands. Infect Immun 1999, 67:2740-2745.
• [13]Abiko Y, Saitoh M, Nishimura M, Yamazaki M, Sawamura D, Kaku T: Role of β-defensins in oral epithelial health and disease. Med Mol Morphol 2007, 40:179-184.
• [14]Tezal M, Sullivan MA, Reid ME, Marshall JR, Hyland A, Loree T, Lillis C, Hauck L, Wactawski-Wende J, Scannapieco FA: Chronic periodontitis and the risk of tongue cancer. Arch Otolaryngol Head Neck Surg 2007, 133:450-454.
• [15]Tezal M, Sullivan MA, Hyland A, Marshall JR, Stoler D, Reid ME, Loree TR, Rigual NR, Merzianu M, Hauck L, Lillis C, Wactawski-Wende J, Scannapieco FA: Chronic periodontitis and the incidence of head and neck squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev 2009, 18:2406-2412.
• [16]Donald CD, Sun CQ, Lim SD, Macoska J, Cohen C, Amin MB, Young AN, Ganz TA, Marshall FF, Petros JA: Cancer-specific loss of beta-defensin 1 in renal and prostatic carcinomas. Lab Invest 2003, 83:501-505.
• [17]Sun CQ, Arnold R, Fernandez-Golarz C, Parrish AB, Almekinder T, He J, Ho SM, Svoboda P, Pohl J, Marshall FF, Petros JA: Human beta-defensin-1, a potential chromosome 8p tumor suppressor: control of transcription and induction of apoptosis in renal cell carcinoma. Cancer Res 2006, 66:8542-8549.
• [18]Joly S, Compton LM, Pujol C, Kurago ZB, Guthmiller JM: Loss of human beta-defensin 1, 2, and 3 expression in oral squamous cell carcinoma. Oral Microbiol Immunol 2009, 24:353-360.
• [19]Wenghoefer M, Pantelis A, Dommisch H, Reich R, Martini M, Allam JP, Novak N, Bergé S, Jepsen S, Winter J: Decreased gene expression of human beta-defensin-1 in the development of squamous cell carcinoma of the oral cavity. Int J Oral Maxillofac Surg 2008, 37:660-663.
• [20]Kesting MR, Loeffelbein DJ, Hasler RJ, Wolff KD, Rittig A, Schulte M, Hirsch T, Wagenpfeil S, Jacobsen F, Steinstraesser L: Expression profile of human beta-defensin 3 in oral squamous cell carcinoma. Cancer Invest 2009, 27:575-581.
• [21]Wenghoefer M, Pantelis A, Najafi T, Deschner J, Allam JP, Novak N, Reich R, Martini M, Bergé S, Fischer HP, Jepsen S, Winter J: Gene expression of oncogenes, antimicrobial peptides, and cytokines in the development of oral leukoplakia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010, 110:351-356.
• [22]Winter J, Pantelis A, Allam JP, Novak N, Reich R, Martini M, Bergé S, Deschner J, Jepsen S, Wenghoefer M: High α-defensin and S100A7 expression and missing DOC-1 down-regulation characterize irritation fibromas of the oral cavity and may counteract malignant transformation. J Craniofac Surg 2011, 22:100-104.
• [23]Schaefer AS, Richter GM, Nothnagel M, Laine ML, Rühling A, Schäfer C, Cordes N, Noack B, Folwaczny M, Glas J, Dörfer C, Dommisch H, Groessner-Schreiber B, Jepsen S, Loos BG, Schreiber S: A 3' UTR transition within DEFB1 is associated with chronic and aggressive periodontitis. Genes Immun 2010, 11:45-54.
• [24]Kraus D, Deschner J, Jäger A, Wenghoefer M, Bayer S, Jepsen S, Allam J, Novak N, Meyer R, Winter J: Human β-defensins differently affect proliferation, differentiation, and mineralization of osteoblast-like MG63 cells. J Cell Physiol 2011.
• [25]Pfaffl MW: A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 2001, 29:2002-2007.
• [26]Hildebrand O: Über angeborene epitheliale Cysten und Fisteln des Halses. Arch Klin Chir 1895, 49:167-206.
• [27]Albrecht H, Arzt L: Beiträge zur Frage der Gewebsverirrung. Papilläre Cystadenome in Lymphdrüsen. Frankfurt Z Pathol 1910, 4:47-69.
• [28]Warthin AS: Papillary cystadenoma lymphomatosum: a rare teratoid of the parotid region. J Cancer Res. 1929, 13:116-125.
• [29]Barnes L, Everson JW, Reichart P, Sidransky D: World Health Organization classification of tumors. Pathology and genetics, head and neck tumours. IARC Press, Lyon; 2005:209-281.
• [30]Faur A, Lazăr E, Cornianu M, Dema A, Vidita CG, Găluşcan A: Warthin tumor: a curious entity-case reports and review of literature. Rom J Morphol Embryol 2009, 50(2):269-273.
• [31]Teymoortash A, Werner JA: Tissue that has lost its track: Warthin's tumour. Virchows Arch 2005, 44(6):585-588. Epub 2005 May 24. Review
• [32]Adria M, Barnes E, Hunt JL: Molecular assessment of allelic loss in Warthin tumors. Mod Pathol 2005, 18(7):964-968.
• [33]Eveson JW, Cawson RA: Salivary gland tumours. A review of 2410 cases with particular reference to histological types, site, age and sex distribution. J Pathol 1985, 146:51-58.
• [34]Winter J, Pantelis A, Reich R, Martini M, Kraus D, Jepsen S, Allam JP, Novak N, Wenghoefer M: Human beta-defensin-1, -2, and -3 exhibit opposite effects on oral squamous cell carcinoma cell proliferation. Cancer Invest 2011, 29:196-201.