Department of Oral and Maxillofacial Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
BioDrugs. 2012 Feb 1;26(1):33-42. doi: 10.2165/11597570-000000000-00000.
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.
The aim of the present study was to investigate whether expression levels of putative pro- or anti-oncogenic hBDs, including hBD-1, -2, -3, and psoriasin/S100A7, are altered in salivary gland tumor tissue as potential targets for molecular-based therapeutic approaches.
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/S100A7 by qrt-PCR was normalized to the endogenous 18S rRNA expression levels.
The results demonstrate the significant downregulation of hBD-1 (p < 0.001), hBD-2 (p = 0.003), hBD-3 (p = 0.002), and psoriasin/S100A7 (p = 0.003) mRNA in human salivary gland tumors compared with healthy control specimens. Protein expression levels of hBD-1, -2, -3, and psoriasin/S100A7 in salivary gland tumor tissue were strongly reduced compared with healthy control specimens.
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.
宿主防御肽（HDPs），包括人β-防御素（hBDs）和角蛋白/ S100A7，发挥先天防御系统的抗菌和免疫调节功能。除了这些功能外，寻找癌症生物标志物已经确定 HDPs 在肿瘤抑制和致癌作用中发挥潜在作用。尽管 HDPs 在唾液腺中高度表达，但它们作为潜在诊断和治疗方法的分子的作用尚未得到分析。
本研究旨在探讨唾液腺癌组织中是否存在潜在的促癌或抑癌 hBDs（包括 hBD-1、-2、-3 和角蛋白/ S100A7）的表达水平发生改变，作为基于分子的治疗方法的潜在靶点。
我们通过比较 58 例患者的唾液腺癌组织样本与健康对照样本，通过定量实时聚合酶链反应（qrt-PCR）和免疫组织化学分析了 hBD-1、-2、-3 和角蛋白/ S100A7 的表达水平。 hBD-1、-2、-3 和角蛋白/ S100A7 的表达水平通过 qrt-PCR 归一化为内源性 18S rRNA 表达水平。
结果表明，与健康对照标本相比，人类唾液腺癌组织中 hBD-1（p <0.001）、hBD-2（p =0.003）、hBD-3（p =0.002）和角蛋白/ S100A7（p =0.003）的 mRNA 显著下调。与健康对照标本相比，唾液腺癌组织中 hBD-1、-2、-3 和角蛋白/ S100A7 的蛋白表达水平明显降低。
数据表明先天防御系统在唾液腺癌形成中具有潜在作用。鉴定免疫调节分子作为诊断生物标志物或治疗靶点可为基于分子的诊断和治疗提供新方法，以治疗唾液腺癌以及其他恶性肿瘤。我们建议考虑使用 HDPs 进行基于分子的治疗方法。
