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Increased matrix metalloproteinase activation in esophageal squamous cell carcinoma

BACKGROUND: 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...

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Autores principales: Mukherjee, Sumana, Roth, Mark J, Dawsey, Sanford M, Yan, Wusheng, Rodriguez-Canales, Jaime, Erickson, Heidi S, Hu, Nan, Goldstein, Alisa M, Taylor, Philip R, Richardson, Annely M, Tangrea, Michael A, Chuaqui, Rodrigo F, Emmert-Buck, Michael R
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2958908/
https://www.ncbi.nlm.nih.gov/pubmed/20920372
http://dx.doi.org/10.1186/1479-5876-8-91
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author Mukherjee, Sumana
Roth, Mark J
Dawsey, Sanford M
Yan, Wusheng
Rodriguez-Canales, Jaime
Erickson, Heidi S
Hu, Nan
Goldstein, Alisa M
Taylor, Philip R
Richardson, Annely M
Tangrea, Michael A
Chuaqui, Rodrigo F
Emmert-Buck, Michael R
author_facet Mukherjee, Sumana
Roth, Mark J
Dawsey, Sanford M
Yan, Wusheng
Rodriguez-Canales, Jaime
Erickson, Heidi S
Hu, Nan
Goldstein, Alisa M
Taylor, Philip R
Richardson, Annely M
Tangrea, Michael A
Chuaqui, Rodrigo F
Emmert-Buck, Michael R
author_sort Mukherjee, Sumana
collection PubMed
description BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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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spelling pubmed-29589082010-10-22 Increased matrix metalloproteinase activation in esophageal squamous cell carcinoma Mukherjee, Sumana Roth, Mark J Dawsey, Sanford M Yan, Wusheng Rodriguez-Canales, Jaime Erickson, Heidi S Hu, Nan Goldstein, Alisa M Taylor, Philip R Richardson, Annely M Tangrea, Michael A Chuaqui, Rodrigo F Emmert-Buck, Michael R J Transl Med Research BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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. BioMed Central 2010-10-05 /pmc/articles/PMC2958908/ /pubmed/20920372 http://dx.doi.org/10.1186/1479-5876-8-91 Text en Copyright ©2010 Mukherjee et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 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.
spellingShingle Research
Mukherjee, Sumana
Roth, Mark J
Dawsey, Sanford M
Yan, Wusheng
Rodriguez-Canales, Jaime
Erickson, Heidi S
Hu, Nan
Goldstein, Alisa M
Taylor, Philip R
Richardson, Annely M
Tangrea, Michael A
Chuaqui, Rodrigo F
Emmert-Buck, Michael R
Increased matrix metalloproteinase activation in esophageal squamous cell carcinoma
title Increased matrix metalloproteinase activation in esophageal squamous cell carcinoma
title_full Increased matrix metalloproteinase activation in esophageal squamous cell carcinoma
title_fullStr Increased matrix metalloproteinase activation in esophageal squamous cell carcinoma
title_full_unstemmed Increased matrix metalloproteinase activation in esophageal squamous cell carcinoma
title_short Increased matrix metalloproteinase activation in esophageal squamous cell carcinoma
title_sort increased matrix metalloproteinase activation in esophageal squamous cell carcinoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2958908/
https://www.ncbi.nlm.nih.gov/pubmed/20920372
http://dx.doi.org/10.1186/1479-5876-8-91
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