Expression Profiles and Clinical Correlations of Degradome Components in the Tumor Microenvironment of Head and Neck Squamous Cell Carcinoma
Expression Profiles and Clinical Correlations of Degradome Components in the Tumor Microenvironment of Head and Neck Squamous Cell Carcinoma
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DOI：
10.1158/1078-0432.ccr-09-2525
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发表时间：
2010-04-01
影响因子：
11.5
通讯作者：
Kahari, Veli-Matti
中科院分区：
文献类型：
--
作者：
Stokes, Angela;Joutsa, Juho;Kahari, Veli-Matti
目的：头颈部鳞状细胞癌（HNSCC）的特点是发病率和死亡率高，主要是由于这些肿瘤的高侵袭性和转移潜力，高复发率和低治疗反应。蛋白酶与包括HNSCC在内的多种肿瘤的肿瘤生长和转移的几个方面有关。蛋白酶[基质金属蛋白酶（MMPs），A去整合素和金属蛋白酶（ADAM），和具有血小板反应蛋白基序的ADAM（ADAMTSs）]及其抑制剂[金属蛋白酶组织抑制剂（TIMPs）]使用定量实时逆转录-对来自83名HNSCC患者的代表肿瘤（n = 83）、侵袭性边缘（n = 41）和邻近组织（n = 41）的大量组织样本、沿着正常组织对照（n = 13）以及从34名HNSCC患者的肿瘤建立的细胞系进行PCR分析。结果显示，在肿瘤组织和肿瘤周围邻近组织中，几种蛋白酶的基因表达特异性升高，包括MMP 1、MMP 3、MMP 10和MMP 13。此外，结果鉴定了几种新的HNSCC相关蛋白酶，包括ADAM8、ADAM9、ADAM17、ADAM28、ADAMTS1、ADAMTS8和ADAMTS15。基于临床参数的蛋白酶表达也存在显著差异，即，肿瘤位置、分级和局部浸润。MMP 13在大的（> 4cm）局部浸润性肿瘤中的表达明显高于小的（P <0.05）。MMP 9在有局部转移的肿瘤中表达明显降低，而ADAM 8在有转移的肿瘤中表达明显升高（P <0.001）。结论：HNSCC降解产物是一种有价值的诊断、预测和预后的分子标志物。临床癌症研究; 16（7）; 2022 - 35。（C）2010年AACR。
Purpose: Head and neck squamous cell carcinomas (HNSCC) are characterized by high morbidity and mortality, largely due to the high invasive and metastatic potential of these tumors, high recurrence rates, and low treatment responses. Proteinases have been implicated in several aspects of tumor growth and metastasis in a broad range of tumors including HNSCC.Experimental Design: Comprehensive expression profiling of proteinases [matrix metalloproteinases (MMPs), A disintegrin and metalloproteinase (ADAMs), and ADAMs with thrombospondin motif (ADAMTSs)] and their inhibitors [tissue inhibitor of metalloproteinases (TIMPs)] was done using quantitative real-time reverse transcription-PCR analysis of a large cohort of tissue samples representing the tumor (n = 83), the invasive margin (n = 41), and the adjacent tissue (n = 41) from 83 HNSCC patients, along with normal tissue controls (n = 13), as well as cell lines established from tumors of 34 HNSCC patients.Results: The results show specifically elevated gene expression of several proteinases, including MMP1, MMP3, MMP10, and MMP13 within tumor tissue and peritumoral adjacent tissue. In addition, the results identify several novel HNSCC-associated proteinases, including ADAM8, ADAM9, ADAM17, ADAM28, ADAMTS1, ADAMTS8, and ADAMTS15. There were also significant differences in proteinase expression based on clinical parameters, i.e., tumor location, grade, and local invasion. MMP13 expression was significantly higher in large (>4 cm) locally invasive tumors (P < 0.05). MMP9 expression was significantly decreased in tumors with regional metastasis, whereas increased expression of ADAM8 was noted in the metastatic tumors (P < 0.001 for both).Conclusions: These findings suggest the HNSCC degradome as a valuable source of diagnostic, predictive, and prognostic molecular markers for these malignant tumors. Clin Cancer Res; 16(7); 2022-35. (C)2010 AACR.