Increased matrix metalloproteinase activation in esophageal squamous cell carcinoma.
Increased matrix metalloproteinase activation in esophageal squamous cell carcinoma.
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DOI：
10.1186/1479-5876-8-91
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发表时间：
2010-10-05
影响因子：
7.4
通讯作者：
Emmert-Buck MR
中科院分区：
文献类型：
--
作者：
Mukherjee S;Roth MJ;Dawsey SM;Yan W;Rodriguez-Canales J;Erickson HS;Hu N;Goldstein AM;Taylor PR;Richardson AM;Tangrea MA;Chuaqui RF;Emmert-Buck MR
食管鳞状细胞癌（ESCC）通常无症状，直到无法治愈才被发现。细胞学筛查是早期检测食管鳞癌的一种策略，在以前的研究中已经显示出希望，尽管需要提高灵敏度和特异性。蛋白酶通过促进肿瘤侵袭和转移来调节癌症进展。在目前的研究中，基质金属蛋白酶（MMPs）的研究，在寻找新的早期检测标志物ESCC。采用酶谱法检测了24例配对正常食管和ESCC中MMPs的蛋白表达水平，并在激光捕获显微切割（LCM）后的一个样本中检测了肿瘤相关基质和肿瘤上皮中MMPs的蛋白表达水平。通过定量逆转录聚合酶链反应（qRT-PCR）进一步分析5例上皮和间质中MMP-3和MMP-10的转录本。明胶酶谱显示24例癌症病例中的每一个的大小对应于MMP-2、MMP-3、MMP-9和MMP-10酶的条带。MMP水平在肿瘤中倾向于高于配对的正常组织;然而，只有对应于MMP-3和MMP-10的活化形式的45 kDa条带在所有24个肿瘤中强烈表达，而在配对的正常病灶中很少或没有表达。基于LCM的分析显示，45 kDA带存在于肿瘤微环境的基质和上皮成分中，并且对于每个隔室，MMP-3和MMP-10 mRNA水平在肿瘤中高于配对的正常组织。MMPs水平的增加发生在ESCC中，表明它们的上调在食管肿瘤发生中是重要的。上调的基因产物有可能作为临床早期检测的标志物。
Esophageal squamous cell carcinomas (ESCC) are usually asymptomatic and go undetected until they are incurable. Cytological screening is one strategy to detect ESCC at an early stage and has shown promise in previous studies, although improvement in sensitivity and specificity are needed. Proteases modulate cancer progression by facilitating tumor invasion and metastasis. In the current study, matrix metalloproteinases (MMPs) were studied in a search for new early detection markers for ESCC. Protein expression levels of MMPs were measured using zymography in 24 cases of paired normal esophagus and ESCC, and in the tumor-associated stroma and tumor epithelium in one sample after laser capture microdissection (LCM). MMP-3 and MMP-10 transcripts in both the epithelium and stroma in five cases were further analyzed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Gelatin zymography showed bands corresponding in size to MMP-2, MMP-3, MMP-9, and MMP-10 enzymes in each of the 24 cancer cases. MMP levels tended to be higher in tumors than paired normal tissue; however, only the 45 kDa band that corresponds to the activated form of MMP-3 and MMP-10 was strongly expressed in all 24 tumors with little or no expression in the paired normal foci. LCM-based analysis showed the 45 kDA band to be present in both the stromal and epithelial components of the tumor microenvironment, and that MMP-3 and MMP-10 mRNA levels were higher in tumors than paired normal tissues for each compartment. Increased levels of MMPs occur in ESCC suggesting their up-regulation is important in esophageal tumorigenesis. The up-regulated gene products have the potential to serve as early detection markers in the clinic.
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影响因子：
5
作者：
Erickson, Heidi S.;Albert, Paul S.;Emmert-Buck, Michael R.
通讯作者：
Emmert-Buck, Michael R.
影响因子：
6.2
作者：
Ishibashi, Y;Matsumoto, T;Urashima, M
通讯作者：
Urashima, M
影响因子：
254.7
作者：
Parkin, DM;Bray, F;Pisani, P
通讯作者：
Pisani, P
DOI：
10.1007/s00432-003-0500-4
发表时间：
2004-01-01
影响因子：
3.6
作者：
Samantaray, S;Sharma, R;Ralhan, R
通讯作者：
Ralhan, R
影响因子：
9.8
作者：
Gu, ZD;Li, JY;Chen, KN
通讯作者：
Chen, KN