Human β-Defensins and Psoriasin/S100A7 Expression in Salivary Glands: Anti-Oncogenic Molecules for Potential Therapeutic Approaches

Background Host defence peptides (HDPs), including human β-defensins (hBDs) and psoriasin/S100A7, exert antimicrobial and immunoregulatory functions of the innate defense system. In addition to these functions, the search for cancer biomarkers has identified HDPs as playing a potential role in both...

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Veröffentlicht in:BioDrugs : clinical immunotherapeutics, biopharmaceuticals, and gene therapy biopharmaceuticals, and gene therapy, 2012-02, Vol.26 (1), p.33-42
Hauptverfasser: Kesting, Marco R., Stoeckelhuber, Mechthild, Kuppek, Alexandra, Hasler, Rafael, Rohleder, Nils, Wolff, Klaus-Dietrich, Nieberler, Markus
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container_title BioDrugs : clinical immunotherapeutics, biopharmaceuticals, and gene therapy
container_volume 26
creator Kesting, Marco R.
Stoeckelhuber, Mechthild
Kuppek, Alexandra
Hasler, Rafael
Rohleder, Nils
Wolff, Klaus-Dietrich
Nieberler, Markus
description Background Host defence peptides (HDPs), including human β-defensins (hBDs) and psoriasin/S100A7, exert antimicrobial and immunoregulatory functions of the innate defense system. In addition to these functions, the search for cancer biomarkers has identified HDPs as playing a potential role in both tumor suppression and oncogenesis. Although HDPs are highly expressed in salivary glands, their role as molecules for potential diagnostic and therapeutic approaches has not yet been analyzed. Objective The aim of the present study was to investigate whether expression levels of putative pro- or antioncogenic hBDs, including hBD-1, -2, -3, and psoriasin/S 100A7, are altered in salivary gland tumor tissue as potential targets for molecular-based therapeutic approaches. Methods We analyzed the expression levels of hBD-1, -2, -3, and psoriasin/S100A7 by quantitative real-time polymerase chain reaction (qrt-PCR) and immunohistochemistry in a case control study by comparing salivary gland tumor samples relative to healthy control specimens from 58 patients. Expression level analysis of hBD-1, -2, -3, and psoriasin/S 100A7 by qrt-PCR was normalized to the endogenous 18S rRNA expression levels. Results The results demonstrate the significant downregulation of hBD-1 (p
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In addition to these functions, the search for cancer biomarkers has identified HDPs as playing a potential role in both tumor suppression and oncogenesis. Although HDPs are highly expressed in salivary glands, their role as molecules for potential diagnostic and therapeutic approaches has not yet been analyzed. Objective The aim of the present study was to investigate whether expression levels of putative pro- or antioncogenic hBDs, including hBD-1, -2, -3, and psoriasin/S 100A7, are altered in salivary gland tumor tissue as potential targets for molecular-based therapeutic approaches. Methods We analyzed the expression levels of hBD-1, -2, -3, and psoriasin/S100A7 by quantitative real-time polymerase chain reaction (qrt-PCR) and immunohistochemistry in a case control study by comparing salivary gland tumor samples relative to healthy control specimens from 58 patients. Expression level analysis of hBD-1, -2, -3, and psoriasin/S 100A7 by qrt-PCR was normalized to the endogenous 18S rRNA expression levels. Results The results demonstrate the significant downregulation of hBD-1 (p&lt;0.001), hBD-2 (p = 0.003), hBD-3 (p = 0.002), and psoriasin/S 100A7 (p = 0.003) mRNA in human salivary gland tumors compared with healthy control specimens. Protein expression levels of hBD-1, -2, -3, and psoriasin/S 100A7 in salivary gland tumor tissue were strongly reduced compared with healthy control specimens. Conclusion The data indicates a putative role of the innate defense system in salivary gland tumor formation. The identification of immunoregulatory molecules as diagnostic biomarkers or therapeutic targets could provide new approaches for molecular-based diagnostic and therapeutic support to treat salivary gland tumors as well as other malignancies. We suggest that HDPs should be taken into consideration for use in molecular-based therapeutic approaches.</description><identifier>ISSN: 1173-8804</identifier><identifier>EISSN: 1179-190X</identifier><identifier>DOI: 10.2165/11597570-000000000-00000</identifier><identifier>PMID: 22149099</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies ; beta-Defensins - biosynthesis ; Biomarkers, Tumor - biosynthesis ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Case-Control Studies ; Child ; Down-Regulation ; Female ; Humans ; Male ; Middle Aged ; Molecular Medicine ; Original Research Article ; Pharmacotherapy ; S100 Calcium Binding Protein A7 ; S100 Proteins - biosynthesis ; Salivary Gland Neoplasms - metabolism ; Salivary Glands - metabolism</subject><ispartof>BioDrugs : clinical immunotherapeutics, biopharmaceuticals, and gene therapy, 2012-02, Vol.26 (1), p.33-42</ispartof><rights>Adis Data Information BV 2012</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c309t-1ed1ae948ae0cf3b5ed50fa5863b144a763af2c850580ff8c7504360c4a2f973</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.2165/11597570-000000000-00000$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.2165/11597570-000000000-00000$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22149099$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kesting, Marco R.</creatorcontrib><creatorcontrib>Stoeckelhuber, Mechthild</creatorcontrib><creatorcontrib>Kuppek, Alexandra</creatorcontrib><creatorcontrib>Hasler, Rafael</creatorcontrib><creatorcontrib>Rohleder, Nils</creatorcontrib><creatorcontrib>Wolff, Klaus-Dietrich</creatorcontrib><creatorcontrib>Nieberler, Markus</creatorcontrib><title>Human β-Defensins and Psoriasin/S100A7 Expression in Salivary Glands: Anti-Oncogenic Molecules for Potential Therapeutic Approaches</title><title>BioDrugs : clinical immunotherapeutics, biopharmaceuticals, and gene therapy</title><addtitle>BioDrugs</addtitle><addtitle>BioDrugs</addtitle><description>Background Host defence peptides (HDPs), including human β-defensins (hBDs) and psoriasin/S100A7, exert antimicrobial and immunoregulatory functions of the innate defense system. In addition to these functions, the search for cancer biomarkers has identified HDPs as playing a potential role in both tumor suppression and oncogenesis. Although HDPs are highly expressed in salivary glands, their role as molecules for potential diagnostic and therapeutic approaches has not yet been analyzed. Objective The aim of the present study was to investigate whether expression levels of putative pro- or antioncogenic hBDs, including hBD-1, -2, -3, and psoriasin/S 100A7, are altered in salivary gland tumor tissue as potential targets for molecular-based therapeutic approaches. Methods We analyzed the expression levels of hBD-1, -2, -3, and psoriasin/S100A7 by quantitative real-time polymerase chain reaction (qrt-PCR) and immunohistochemistry in a case control study by comparing salivary gland tumor samples relative to healthy control specimens from 58 patients. Expression level analysis of hBD-1, -2, -3, and psoriasin/S 100A7 by qrt-PCR was normalized to the endogenous 18S rRNA expression levels. Results The results demonstrate the significant downregulation of hBD-1 (p&lt;0.001), hBD-2 (p = 0.003), hBD-3 (p = 0.002), and psoriasin/S 100A7 (p = 0.003) mRNA in human salivary gland tumors compared with healthy control specimens. Protein expression levels of hBD-1, -2, -3, and psoriasin/S 100A7 in salivary gland tumor tissue were strongly reduced compared with healthy control specimens. Conclusion The data indicates a putative role of the innate defense system in salivary gland tumor formation. The identification of immunoregulatory molecules as diagnostic biomarkers or therapeutic targets could provide new approaches for molecular-based diagnostic and therapeutic support to treat salivary gland tumors as well as other malignancies. 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Stoeckelhuber, Mechthild ; Kuppek, Alexandra ; Hasler, Rafael ; Rohleder, Nils ; Wolff, Klaus-Dietrich ; Nieberler, Markus</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c309t-1ed1ae948ae0cf3b5ed50fa5863b144a763af2c850580ff8c7504360c4a2f973</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antibodies</topic><topic>beta-Defensins - biosynthesis</topic><topic>Biomarkers, Tumor - biosynthesis</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Case-Control Studies</topic><topic>Child</topic><topic>Down-Regulation</topic><topic>Female</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Molecular Medicine</topic><topic>Original Research Article</topic><topic>Pharmacotherapy</topic><topic>S100 Calcium Binding Protein A7</topic><topic>S100 Proteins - biosynthesis</topic><topic>Salivary Gland Neoplasms - metabolism</topic><topic>Salivary Glands - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kesting, Marco R.</creatorcontrib><creatorcontrib>Stoeckelhuber, Mechthild</creatorcontrib><creatorcontrib>Kuppek, Alexandra</creatorcontrib><creatorcontrib>Hasler, Rafael</creatorcontrib><creatorcontrib>Rohleder, Nils</creatorcontrib><creatorcontrib>Wolff, Klaus-Dietrich</creatorcontrib><creatorcontrib>Nieberler, Markus</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>BioDrugs : clinical immunotherapeutics, biopharmaceuticals, and gene therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kesting, Marco R.</au><au>Stoeckelhuber, Mechthild</au><au>Kuppek, Alexandra</au><au>Hasler, Rafael</au><au>Rohleder, Nils</au><au>Wolff, Klaus-Dietrich</au><au>Nieberler, Markus</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human β-Defensins and Psoriasin/S100A7 Expression in Salivary Glands: Anti-Oncogenic Molecules for Potential Therapeutic Approaches</atitle><jtitle>BioDrugs : clinical immunotherapeutics, biopharmaceuticals, and gene therapy</jtitle><stitle>BioDrugs</stitle><addtitle>BioDrugs</addtitle><date>2012-02-01</date><risdate>2012</risdate><volume>26</volume><issue>1</issue><spage>33</spage><epage>42</epage><pages>33-42</pages><issn>1173-8804</issn><eissn>1179-190X</eissn><abstract>Background Host defence peptides (HDPs), including human β-defensins (hBDs) and psoriasin/S100A7, exert antimicrobial and immunoregulatory functions of the innate defense system. In addition to these functions, the search for cancer biomarkers has identified HDPs as playing a potential role in both tumor suppression and oncogenesis. Although HDPs are highly expressed in salivary glands, their role as molecules for potential diagnostic and therapeutic approaches has not yet been analyzed. Objective The aim of the present study was to investigate whether expression levels of putative pro- or antioncogenic hBDs, including hBD-1, -2, -3, and psoriasin/S 100A7, are altered in salivary gland tumor tissue as potential targets for molecular-based therapeutic approaches. Methods We analyzed the expression levels of hBD-1, -2, -3, and psoriasin/S100A7 by quantitative real-time polymerase chain reaction (qrt-PCR) and immunohistochemistry in a case control study by comparing salivary gland tumor samples relative to healthy control specimens from 58 patients. Expression level analysis of hBD-1, -2, -3, and psoriasin/S 100A7 by qrt-PCR was normalized to the endogenous 18S rRNA expression levels. Results The results demonstrate the significant downregulation of hBD-1 (p&lt;0.001), hBD-2 (p = 0.003), hBD-3 (p = 0.002), and psoriasin/S 100A7 (p = 0.003) mRNA in human salivary gland tumors compared with healthy control specimens. Protein expression levels of hBD-1, -2, -3, and psoriasin/S 100A7 in salivary gland tumor tissue were strongly reduced compared with healthy control specimens. Conclusion The data indicates a putative role of the innate defense system in salivary gland tumor formation. The identification of immunoregulatory molecules as diagnostic biomarkers or therapeutic targets could provide new approaches for molecular-based diagnostic and therapeutic support to treat salivary gland tumors as well as other malignancies. We suggest that HDPs should be taken into consideration for use in molecular-based therapeutic approaches.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>22149099</pmid><doi>10.2165/11597570-000000000-00000</doi><tpages>10</tpages></addata></record>
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source MEDLINE; SpringerLink Journals - AutoHoldings
subjects Adolescent
Adult
Aged
Aged, 80 and over
Antibodies
beta-Defensins - biosynthesis
Biomarkers, Tumor - biosynthesis
Biomedical and Life Sciences
Biomedicine
Cancer Research
Case-Control Studies
Child
Down-Regulation
Female
Humans
Male
Middle Aged
Molecular Medicine
Original Research Article
Pharmacotherapy
S100 Calcium Binding Protein A7
S100 Proteins - biosynthesis
Salivary Gland Neoplasms - metabolism
Salivary Glands - metabolism
title Human β-Defensins and Psoriasin/S100A7 Expression in Salivary Glands: Anti-Oncogenic Molecules for Potential Therapeutic Approaches
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