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Journal of Translational Medicine

, 8:91

Cancer microenvironment

Abstract

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.

Electronic supplementary materialThe online version of this article doi:10.1186-1479-5876-8-91 contains supplementary material, which is available to authorized users.

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Autor: Sumana Mukherjee - Mark J Roth - Sanford M Dawsey - Wusheng Yan - Jaime Rodriguez-Canales - Heidi S Erickson - Nan Hu -

Fuente: https://link.springer.com/







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