MMP9 expression in oesophageal adenocarcinoma is upregulated with visceral obesity and is associated with poor tumour differentiation.

Hdl Handle:
http://hdl.handle.net/10147/230673
Title:
MMP9 expression in oesophageal adenocarcinoma is upregulated with visceral obesity and is associated with poor tumour differentiation.
Authors:
Allott, Emma H; Lysaght, Joanne; Cathcart, Mary Clare; Donohoe, Claire L; Cummins, Robert; McGarrigle, Sarah A; Kay, Elaine; Reynolds, John V; Pidgeon, Graham P
Affiliation:
Department of Surgery, Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland.
Citation:
MMP9 expression in oesophageal adenocarcinoma is upregulated with visceral obesity and is associated with poor tumour differentiation. 2011: Mol. Carcinog.
Journal:
Molecular carcinogenesis
Issue Date:
28-Nov-2011
URI:
http://hdl.handle.net/10147/230673
DOI:
10.1002/mc.21840
PubMed ID:
22121096
Abstract:
Overweight and obesity is linked to increased incidence and mortality of many cancer types. Of all cancers, oesophageal adenocarcinoma (OAC) displays one of the strongest epidemiological links with obesity, accounting for up to 40% of cases, but molecular pathways driving this association remain largely unknown. This study aimed to elucidate mechanisms underpinning the association of obesity and cancer, and to determine if visceral obesity is associated with aggressive tumour biology in OAC. Following co-culture with visceral adipose tissue explants, expression of genes involved in tumour cell invasion and metastasis (matrix metalloproteinase (MMP)2 and MMP9) were upregulated between 10-fold (MMP2) and 5000-fold (MMP9), and expression of tumour suppressor p53 was downregulated 2-fold in OAC cell lines. Western blotting confirmed these results at the protein level, while zymographic analysis detected increased activity of MMPs in OAC cell lines following co-culture with adipose tissue explants. When OAC cell lines were cultured with adipose tissue conditioned media (ACM) from visceral adipose tissue, increased proliferative, migratory and invasive capacity of tumour cells was observed. In OAC patient tumour biopsies, elevated gene expression of MMP9 was associated with visceral obesity, measured by visceral fat area, while increased gene expression of MMP9 and decreased gene expression of tumour suppressor p53 was associated with poor tumour differentiation. These novel data highlight an important role for visceral obesity in upregulation of pro-tumour pathways contributing to aggressive tumour biology, and may ultimately lead to development of stratified treatment for viscerally obese OAC patients. © 2011 Wiley Periodicals, Inc.
Item Type:
Article
Language:
en
ISSN:
1098-2744

Full metadata record

DC FieldValue Language
dc.contributor.authorAllott, Emma Hen_GB
dc.contributor.authorLysaght, Joanneen_GB
dc.contributor.authorCathcart, Mary Clareen_GB
dc.contributor.authorDonohoe, Claire Len_GB
dc.contributor.authorCummins, Roberten_GB
dc.contributor.authorMcGarrigle, Sarah Aen_GB
dc.contributor.authorKay, Elaineen_GB
dc.contributor.authorReynolds, John Ven_GB
dc.contributor.authorPidgeon, Graham Pen_GB
dc.date.accessioned2012-06-25T16:26:50Z-
dc.date.available2012-06-25T16:26:50Z-
dc.date.issued2011-11-28-
dc.identifier.citationMMP9 expression in oesophageal adenocarcinoma is upregulated with visceral obesity and is associated with poor tumour differentiation. 2011: Mol. Carcinog.en_GB
dc.identifier.issn1098-2744-
dc.identifier.pmid22121096-
dc.identifier.doi10.1002/mc.21840-
dc.identifier.urihttp://hdl.handle.net/10147/230673-
dc.description.abstractOverweight and obesity is linked to increased incidence and mortality of many cancer types. Of all cancers, oesophageal adenocarcinoma (OAC) displays one of the strongest epidemiological links with obesity, accounting for up to 40% of cases, but molecular pathways driving this association remain largely unknown. This study aimed to elucidate mechanisms underpinning the association of obesity and cancer, and to determine if visceral obesity is associated with aggressive tumour biology in OAC. Following co-culture with visceral adipose tissue explants, expression of genes involved in tumour cell invasion and metastasis (matrix metalloproteinase (MMP)2 and MMP9) were upregulated between 10-fold (MMP2) and 5000-fold (MMP9), and expression of tumour suppressor p53 was downregulated 2-fold in OAC cell lines. Western blotting confirmed these results at the protein level, while zymographic analysis detected increased activity of MMPs in OAC cell lines following co-culture with adipose tissue explants. When OAC cell lines were cultured with adipose tissue conditioned media (ACM) from visceral adipose tissue, increased proliferative, migratory and invasive capacity of tumour cells was observed. In OAC patient tumour biopsies, elevated gene expression of MMP9 was associated with visceral obesity, measured by visceral fat area, while increased gene expression of MMP9 and decreased gene expression of tumour suppressor p53 was associated with poor tumour differentiation. These novel data highlight an important role for visceral obesity in upregulation of pro-tumour pathways contributing to aggressive tumour biology, and may ultimately lead to development of stratified treatment for viscerally obese OAC patients. © 2011 Wiley Periodicals, Inc.en_GB
dc.languageENG-
dc.language.isoenen
dc.rightsArchived with thanks to Molecular carcinogenesisen_GB
dc.titleMMP9 expression in oesophageal adenocarcinoma is upregulated with visceral obesity and is associated with poor tumour differentiation.en_GB
dc.typeArticleen
dc.contributor.departmentDepartment of Surgery, Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland.en_GB
dc.identifier.journalMolecular carcinogenesisen_GB
dc.description.provinceLeinsteren

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