BACKGROUND AND AIMS: Matrix metalloproteinase-7 (MMP-7) is important in normal and pathological remodelling of epithelial-matrix interactions, and is upregulated in gastric cancer. Helicobacter pylori infection is the first stage in gastric carcinogenesis, and therefore our aim was to determine if H pylori upregulated gastric MMP-7 expression and if this was affected by strain virulence. METHODS: We took gastric biopsy specimens at endoscopy from H pylori infected (n = 17) and uninfected (n = 18) patients and assessed MMP-7 expression by ELISA, real time polymerase chain reaction (PCR), and immunohistochemistry (concentrating on epithelial cells in the proliferative zone). We PCR typed H pylori for cagE and vacA. We performed H pylori/cell line coculture studies with wild-type pathogenic and non-pathogenic H pylori strains and with CagE(-) and VacA(-) isogenic mutants. RESULTS: Gastric biopsy specimens from H pylori+ patients expressed higher levels of MMP-7 at the protein and mRNA levels in the antrum and corpus (for example, by ELISA: H pylori+ 0.182 OD units vH pylori- 0.059; p = 0.009 antrum). Epithelial cells from H pylori+ patients stained more intensely for MMP-7 than those from uninfected patients, including in the proliferative zone containing pluripotent cells (p<0.03 antrum, p<0.04 body). Upregulation of MMP-7 in epithelial cells was confirmed at the protein and mRNA levels by H pylori/cell line coculture. These experiments also showed that MMP-7 upregulation was dependent on an intact H pyloricag pathogenicity island but not on the vacuolating cytotoxin. CONCLUSION: We speculate that increased expression of MMP-7 in H pylori gastritis may contribute to gastric carcinogenesis.
BACKGROUND AND AIMS: Matrix metalloproteinase-7 (MMP-7) is important in normal and pathological remodelling of epithelial-matrix interactions, and is upregulated in gastric cancer. Helicobacter pylori infection is the first stage in gastric carcinogenesis, and therefore our aim was to determine if H pylori upregulated gastric MMP-7 expression and if this was affected by strain virulence. METHODS: We took gastric biopsy specimens at endoscopy from H pylori infected (n = 17) and uninfected (n = 18) patients and assessed MMP-7 expression by ELISA, real time polymerase chain reaction (PCR), and immunohistochemistry (concentrating on epithelial cells in the proliferative zone). We PCR typed H pylori for cagE and vacA. We performed H pylori/cell line coculture studies with wild-type pathogenic and non-pathogenic H pylori strains and with CagE(-) and VacA(-) isogenic mutants. RESULTS: Gastric biopsy specimens from H pylori+ patients expressed higher levels of MMP-7 at the protein and mRNA levels in the antrum and corpus (for example, by ELISA: H pylori+ 0.182 OD units vH pylori- 0.059; p = 0.009 antrum). Epithelial cells from H pylori+ patients stained more intensely for MMP-7 than those from uninfected patients, including in the proliferative zone containing pluripotent cells (p<0.03 antrum, p<0.04 body). Upregulation of MMP-7 in epithelial cells was confirmed at the protein and mRNA levels by H pylori/cell line coculture. These experiments also showed that MMP-7 upregulation was dependent on an intact H pyloricag pathogenicity island but not on the vacuolating cytotoxin. CONCLUSION: We speculate that increased expression of MMP-7 in H pylorigastritis may contribute to gastric carcinogenesis.
Authors: H C Crawford; B M Fingleton; L A Rudolph-Owen; K J Goss; B Rubinfeld; P Polakis; L M Matrisian Journal: Oncogene Date: 1999-05-06 Impact factor: 9.867
Authors: P Guilford; J Hopkins; J Harraway; M McLeod; N McLeod; P Harawira; H Taite; R Scoular; A Miller; A E Reeve Journal: Nature Date: 1998-03-26 Impact factor: 49.962
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Authors: V Noë; B Fingleton; K Jacobs; H C Crawford; S Vermeulen; W Steelant; E Bruyneel; L M Matrisian; M Mareel Journal: J Cell Sci Date: 2001-01 Impact factor: 5.285
Authors: Yinfei Yin; Anna M Grabowska; Philip A Clarke; Elisabeth Whelband; Karen Robinson; Richard H Argent; Amanda Tobias; Rajendra Kumari; John C Atherton; Susan A Watson Journal: Gut Date: 2010-06-28 Impact factor: 23.059
Authors: Sean Y Kassim; Sina A Gharib; Brigham H Mecham; Timothy P Birkland; William C Parks; John K McGuire Journal: Infect Immun Date: 2007-10-08 Impact factor: 3.441
Authors: Seth R Ogden; Lydia E Wroblewski; Christiane Weydig; Judith Romero-Gallo; Daniel P O'Brien; Dawn A Israel; Uma S Krishna; Barbara Fingleton; Albert B Reynolds; Silja Wessler; Richard M Peek Journal: Mol Biol Cell Date: 2008-07-23 Impact factor: 4.138