Increased matrix metalloproteinase activation in esophageal squamous cell carcinoma

Journal of Translational Medicine

Research

Philip R Taylor¹  Nan Hu¹  Alisa M Goldstein¹  Mark J Roth²  Sanford M Dawsey²  Rodrigo F Chuaqui³  Michael R Emmert-Buck³  Wusheng Yan³  Jaime Rodriguez-Canales³  Michael A Tangrea³  Heidi S Erickson³  Sumana Mukherjee³  Annely M Richardson³ 

[1] Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA;Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA;Pathogenetics Unit, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA;

关键词: Esophageal Squamous Cell Carcinoma;    Laser Capture Microdissection;    Esophageal Squamous Cell Carcinoma Patient;    TaqMan Gene Expression Assay;    Stromal Compartment;   

DOI  :  10.1186/1479-5876-8-91

 received in 2010-03-15, accepted in 2010-10-05,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundEsophageal 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.MethodsProtein 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).ResultsGelatin 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.ConclusionsIncreased 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.

【 授权许可】

Unknown   
© Mukherjee et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.