The Role of Matrix Metalloproteinase-7 in Redefining the Gastric Microenvironment in Response to Helicobacter pylori

McCaig, Catherine; Duval, Cédric; Hemers, Elaine; Steele, Islay; Pritchard, D. Mark; Przemeck, S.M.C.; Dimaline, R.; Ahmed, Saiqa; Bodger, Keith; Kerrigan, David; Wang, Yichen; Dockray, Graham J.; Varró, Andrea

doi:10.1053/j.gastro.2006.02.031

Cited by 89 publications

(108 citation statements)

References 35 publications

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“…Gastrin has been reported to have a growth factor-like effect on gastric cells, and we have previously reported that Reg I, amphiregulin, and some of MMP family members, such as MMP-7, -9, -10, and -13 were up-regulated in INS-GAS mice of FVB/N background. 23,26,27 In the current study, we confirmed up-regulation of these genes except MMP-7 and -10 as shown in Figure 6, A-C. Previously we have reported that H. felis or H. pylori infection of INS-GAS male mice in an FVB/N background rapidly leads to corpus gastric cancer at 7 to 8 MPI.…”

Section: Discussionsupporting

confidence: 87%

Gastrin Is an Essential Cofactor for Helicobacter-Associated Gastric Corpus Carcinogenesis in C57BL/6 Mice

Takaishi

Dubeykovskaya

et al. 2009

The American Journal of Pathology

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We have previously described a synergistic interaction between hypergastrinemia and Helicobacter felis infection on gastric corpus carcinogenesis in FVB/N mice housed under specific-pathogen-free conditions. However, gastrin-deficient (GAS-KO) mice on a mixed C57BL/6/129Sv genetic background maintained in conventional housing were reported to develop spontaneous gastric antral tumors. Therefore, we investigated the role of gastrin in Helicobacterassociated gastric carcinogenesis in H. felis-infected mice on a uniform C57BL/6 background housed in specific-pathogen-free conditions. Hypergastrinemic transgenic (INS-GAS) mice, GAS-KO mice, and C57BL/6 wild-type mice were infected with H. felis for either 12 or 18 months. At 12 months postinfection, INS-GAS mice had mild corpus dysplasia, while B6 wild-type mice had either severe gastritis or metaplasia, and GAS-KO mice had only mild to moderate gastritis. At 18 months postinfection, both INS-GAS and B6 wild-type mice had both severe atrophic gastritis and corpus dysplasia, while GAS-KO mice had severe gastritis with mild gastric atrophy, but no corpus dysplasia. In contrast, both GAS-KO and B6 wildtype mice had mild to moderate antral dysplasia, while INS-GAS mice did not. H. felis antral colonization remained stable over time among the three groups of mice. These results point to a distinct effect of gastrin on carcinogenesis of both the gastric corpus and antrum, suggesting that gastrin is an essential cofactor for gastric corpus carcinogenesis in C57BL/6 mice. Gastric cancer remains the second leading cause of cancer-related mortality in the world, although its incidence and mortality rates have been decreasing in the United States over the past 70 years.

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Section: Discussionsupporting

confidence: 87%

Gastrin Is an Essential Cofactor for Helicobacter-Associated Gastric Corpus Carcinogenesis in C57BL/6 Mice

Takaishi

Dubeykovskaya

et al. 2009

The American Journal of Pathology

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“…This suggests that bacteria can alter the tight junctions and penetrate the deeper intercellular spaces down the underlying lamina propria . Moreover, the H. pylori infection increased the MMP‐7 expression, the number of myofibroblasts, and their proliferation and migration 14, 15. High MMP7 expression facilitated cancer invasion and angiogenesis by degrading extracellular matrix macromolecules and connective tissues in vivo.…”

Section: Introductionmentioning

confidence: 99%

Role of Helicobacter pylori infection in cancer‐associated fibroblast‐induced epithelial‐mesenchymal transition in vitro

et al. 2018

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BackgroundMajor human gastrointestinal pathogen Helicobacter pylori (H. pylori) colonizes the gastric mucosa causing inflammation and severe complications including cancer, but the involvement of fibroblasts in the pathogenesis of these disorders in H. pylori‐infected stomach has been little studied. Normal stroma contains few fibroblasts, especially myofibroblasts. Their number rapidly increases in the reactive stroma surrounding inflammatory region and neoplastic tissue; however, the interaction between H. pylori and fibroblasts remains unknown. We determined the effect of coincubation of normal rat gastric fibroblasts with alive H. pylori (cagA+vacA+) and H. pylori (cagA−vacA−) strains on the differentiation of these fibroblasts into cells possessing characteristics of cancer‐associated fibroblasts (CAFs) able to induce epithelial‐mesenchymal transition (EMT) of normal rat gastric epithelial cells (RGM‐1).Materials and MethodsThe panel of CAFs markers mRNA was analyzed in H. pylori (cagA+vacA+)‐infected fibroblasts by RT‐PCR. After insert coculture of differentiated fibroblasts with RGM‐1 cells from 24 up to 48, 72, and 96 hours, the mRNA expression for EMT‐associated genes was analyzed by RT‐PCR.ResultsThe mRNA expression for CAFs markers was significantly increased after 72 hours of infection with H. pylori (cagA+vacA+) but not H. pylori (cagA−vacA−) strain. Following coculture with CAFs, RGM‐1 cells showed significant decrease in E‐cadherin mRNA, and the parallel increase in the expression of Twist and Snail transcription factors mRNA was observed along with the overexpression of mRNAs for TGFβR, HGFR, FGFR, N‐cadherin, vimentin, α‐SMA, VEGF, and integrin‐β1.Conclusion Helicobacter pylori (cagA+vacA+) strain induces differentiation of normal fibroblasts into CAFs, likely to initiate the EMT process in RGM‐1 epithelial cell line.

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“…The unit bases, the glands, are surrounded by a sheath of smooth muscle ␣-actin (SMA)-expressing intestinal subepithelial myofibroblasts, 29 which, at least in the small intestine, link with the thin muscular sheath under the basal lamina called muscularis mucosae. 30 In some pathological conditions of the gastric epithelium, like neo-or metaplasia 31,32 or helicobacter gastritis, 33 these myofibroblasts increase. In polyps of Peutz-Jeghers patients 34 and Lkb1 ϩ/Ϫ mice, 7 thick disorganized bundles of smooth muscle originating from the muscularis mucosae branch like a cauliflower stalk into polyp lobes.…”

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confidence: 99%

Impaired Gastric Gland Differentiation in Peutz-Jeghers Syndrome

Udd

Katajisto

Kyyrönen

et al. 2010

The American Journal of Pathology

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Gastrointestinal hamartomatous polyps in the PeutzJeghers cancer predisposition syndrome and its mouse model (Lkb1؉/؊ ) are presumed to contain all cell types native to the site of their occurrence. This study aimed to explore the pathogenesis of PeutzJeghers syndrome polyposis by characterizing cell types and differentiation of the epithelium of gastric polyps and predisposed mucosa. Both antral and fundic polyps were characterized by a deficit of pepsinogen C-expressing differentiated gland cells (antral gland, mucopeptic, and chief cells); in large fundic polyps, parietal cells were also absent. Gland cell loss was associated with an increase in precursor neck cells, an expansion of the proliferative zone, and an increase in smooth muscle ␣-actin expressing myofibroblasts in the polyp stroma. Lack of pepsinogen C-positive gland cells identified incipient polyps, and even the unaffected mucosa of young predisposed mice displayed an increase in pepsinogen C negative glands (25%; P ‫؍‬ 0045). In addition, in small intestinal polyps, gland cell differentiation was defective, with the absence of Paneth cells. There were no signs of metaplastic differentiation in any of the tissues studied, and both the gastric and small intestinal defects were seen in Lkb1 ؉/؊ mice, as well as polyps from patients with Peutz-Jeghers syndrome. These results identify impaired epithelial differentiation as the earliest pathological sign likely to contribute to tumorigenesis in individuals with inherited Lkb1 mutations. (Am J

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The Role of Matrix Metalloproteinase-7 in Redefining the Gastric Microenvironment in Response to Helicobacter pylori

Cited by 89 publications

References 35 publications

Gastrin Is an Essential Cofactor for Helicobacter-Associated Gastric Corpus Carcinogenesis in C57BL/6 Mice

Gastrin Is an Essential Cofactor for Helicobacter-Associated Gastric Corpus Carcinogenesis in C57BL/6 Mice

Role of Helicobacter pylori infection in cancer‐associated fibroblast‐induced epithelial‐mesenchymal transition in vitro

Impaired Gastric Gland Differentiation in Peutz-Jeghers Syndrome

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