Multiple kallikrein (KLK 5, 7, 8, and 10) expression in squamous cell carcinoma of the oral cavity.
Multiple kallikrein (KLK 5, 7, 8, and 10) expression in squamous cell carcinoma of the oral cavity.
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DOI：
10.14670/hh-24.197
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发表时间：
2009-02
影响因子：
2
通讯作者：
Stack MS
中科院分区：
文献类型：
--
作者：
Pettus JR;Johnson JJ;Shi Z;Davis JW;Koblinski J;Ghosh S;Liu Y;Ravosa MJ;Frazier S;Stack MS
口腔鳞状细胞癌（OSCC）占美国所有癌症死亡的3%，是全球十大癌症之一。在过去的几十年中，5年生存率一直保持在50%的低水平，需要发现侵袭性疾病和治疗靶点的新生物标志物。由于尿型纤溶酶原激活物和受体（uPA/R）在OSCC中的过表达与恶性进展和不良结局相关，因此产生具有uPAR的过表达（SCC 25-uPAR+）或沉默（SCC 25-uPAR-KD）的细胞系。由于SCC 25-uPAR+肿瘤在体外和体内表现得更具侵袭性，因此使用比较cDNA微阵列分析来鉴定可能与侵袭性肿瘤相关的其他基因。鉴定了人组织激肽释放酶家族的四个成员（KLK 5、7、8和10），并使用实时RT-PCR（qPCR）验证和定量基因表达。qPCR分析显示，与SCC 25-uPAR-KD相比，SCC 25-uPAR+中KLK 5、7、8和10的基因表达分别增加2.8、5.3、4.0和3.5倍。免疫组织化学分析表明，在原位小鼠肿瘤和人口腔鳞癌组织中，KLK 5、7、8和10具有强反应性。对照实验显示缺乏对KLK 3（前列腺特异性抗原）的反应性。这些结果表明，激肽释放酶5，7，8和10在人口腔鳞癌中大量表达，并可能与恶性进展有关。
Oral squamous cell carcinoma (OSCC) represents 3% of all cancer deaths in the U.S. and is ranked one of the top 10 cancers worldwide. The 5-year survival rate has remained at a low 50% for the past several decades, necessitating discovery of novel biomarkers of aggressive disease and therapeutic targets. As overexpression of urinary type plasminogen activator and receptor (uPA/R) in OSCC is associated with malignant progression and poor outcome, cell lines were generated with either overexpression (SCC25-uPAR+) or silencing (SCC25-uPAR-KD) of uPAR. As SCC25-uPAR+ tumors behaved more aggressively both in vitro and in vivo, comparative cDNA microarray analysis was used to identify additional genes that may be associated with aggressive tumors. Four members of the human tissue kallikrein family (KLK 5, 7, 8, and 10) were identified and real-time RT-PCR (qPCR) was used to verify and quantify gene expression. qPCR analysis revealed 2.8-, 5.3-, 4.0-, and 3.5-fold increases in gene expression for KLK5, 7, 8, and 10, respectively, in SCC25-uPAR+ versus SCC25-uPAR-KD. Immunohistochemical analysis demonstrated strong reactivity for KLKs 5, 7, 8 and 10 in both orthotopic murine tumors and human OSCC tissues. Control experiments show lack of reactivity against KLK3 (prostate specific antigen). These results demonstrate that kallikreins 5, 7, 8, and 10 are abundantly expressed in human OSCC and may be implicated in malignant progression.