Nitric oxide-mediated invasion in Barrett's high-grade dysplasia and adenocarcinoma.

Abstract:

:Nitric oxide (NO) has been shown to induce double strand DNA breaks in Barrett's oesophagus (BO) and in other cancers has a role in invasion. The specific aims of this study were to investigate whether NO can induce invasion in cells representative of different stages of Barrett's progression and to determine possible underlying mechanisms. Physiological concentrations of NO that mimic luminal production of NO from dietary sources enhanced invasion in cell lines from high-grade dysplasia (GihTERT) and oesophageal adenocarcinoma (FLO) but not a non-dysplastic Barrett's cell line (QhTERT). Real-time reverse transcription-polymerase chain reaction revealed that NO induced expression of matrix metalloproteinase (MMP)-1, -3, -7, -9 and -10 and tissue inhibitor of metalloproteinase (TIMP)-1, -2 and -3 in these cell lines. Furthermore, ex vivo treatment of Barrett's biopsy samples with NO induced increases in MMP-1 and TIMP-1 expression, suggesting that NO enhances invasion through deregulating MMP and TIMP expression in epithelial cells. In keeping with these findings, microarray analysis and immunohistochemistry performed on biopsy samples showed enhanced expression of MMP-1, -3, -7 and -10 and TIMP-1 in the progression from non-dysplastic BO to adenocarcinoma, although this could not be directly attributed to the effect of NO. Thus, NO may play a role in Barrett's carcinogenesis through deregulating MMP and TIMP expression to enhance invasive potential.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Clemons NJ,Shannon NB,Abeyratne LR,Walker CE,Saadi A,O'Donovan ML,Lao-Sirieix PP,Fitzgerald RC

doi

10.1093/carcin/bgq130

subject

Has Abstract

pub_date

2010-09-01 00:00:00

pages

1669-75

issue

9

eissn

0143-3334

issn

1460-2180

pii

bgq130

journal_volume

31

pub_type

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