The role of viral and bacterial pathogens in gastrointestinal cancer

Selgrad, Michael; Malfertheiner, Peter; Fini, Lucia; Goel, Ajay; Boland, C. Richard; Ricciardiello, Luigi

doi:10.1002/jcp.21427

Cited by 43 publications

(46 citation statements)

References 207 publications

(197 reference statements)

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“…Specific agents, such as Helicobacter pylori, human papillomavirus, Epstein-Barr virus, and JC virus, have been directly implicated in the etiopathogenesis of several tumors, including gastrointestinal cancers (31,32).…”

Section: Figurementioning

confidence: 99%

The cytomegalovirus-encoded chemokine receptor US28 promotes intestinal neoplasia in transgenic mice

Bongers¹,

Maussang²,

Muniz³

et al. 2010

J. Clin. Invest.

112

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US28 is a constitutively active chemokine receptor encoded by CMV (also referred to as human herpesvirus 5), a highly prevalent human virus that infects a broad spectrum of cells, including intestinal epithelial cells (IECs). To study the role of US28 in vivo, we created transgenic mice (VS28 mice) in which US28 expression was targeted to IECs. Expression of US28 was detected in all IECs of the small and large intestine, including in cells expressing leucine rich repeat containing GPCR5 (Lgr5), a marker gene of intestinal epithelial stem cells. US28 expression in IECs inhibited glycogen synthase 3β (GSK-3β) function, promoted accumulation of β-catenin protein, and increased expression of Wnt target genes involved in the control of the cell proliferation. VS28 mice showed a hyperplastic intestinal epithelium and, strikingly, developed adenomas and adenocarcinomas by 40 weeks of age. When exposed to an inflammation-driven tumor model (azoxymethane/dextran sodium sulfate), VS28 mice developed a significantly higher tumor burden than control littermates. Transgenic coexpression of the US28 ligand CCL2 (an inflammatory chemokine) increased IEC proliferation as well as tumor burden, suggesting that the oncogenic activity of US28 can be modulated by inflammatory factors. Together, these results indicate that expression of US28 promotes development of intestinal dysplasia and cancer in transgenic mice and suggest that CMV infection may facilitate development of intestinal neoplasia in humans.

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Section: Figurementioning

confidence: 99%

The cytomegalovirus-encoded chemokine receptor US28 promotes intestinal neoplasia in transgenic mice

Bongers¹,

Maussang²,

Muniz³

et al. 2010

J. Clin. Invest.

112

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“…Concurrently, the intestine must tolerate an extensive load of microbiota and is susceptible to various types of acute and chronic infection that can elicit intestinal inflammation. Not surprisingly, alterations in human microbiota, as well as bacterial infections, mainly due to Helicobacter species, have been inextricably linked to gastrointestinal disease and cancer (2)(3)(4). Yet while bacterial infection has been associated with blood cell infiltration and the induction of immune responses, its role in carcinogenesis has not been demonstrated conclusively (3)(4)(5).…”

mentioning

confidence: 99%

“…Not surprisingly, alterations in human microbiota, as well as bacterial infections, mainly due to Helicobacter species, have been inextricably linked to gastrointestinal disease and cancer (2)(3)(4). Yet while bacterial infection has been associated with blood cell infiltration and the induction of immune responses, its role in carcinogenesis has not been demonstrated conclusively (3)(4)(5). In addition, while the roles of the Notch and K-Ras signaling pathways in human colorectal cancer have been unequivocally demonstrated (6,7), the contribution of these pathways in stem cells (SCs) and progenitors in intestinal tumor initiation remains elusive.…”

mentioning

confidence: 99%

“…The evidence that hyperproliferating intestinal SCs and progenitors drive cancer initiation, maintenance, and metastasis (8)(9)(10), and that chronic inflammation has a role in cancer (4,5,11), indicates that under some conditions, hyperproliferation diverts from homeostasis to tumorigenesis. Among the various oncogenes, K-Ras is a commonly identified factor that drives gastrointestinal tumors (6).…”

mentioning

confidence: 99%

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Synergy between bacterial infection and genetic predisposition in intestinal dysplasia

Apidianakis

Pitsouli²,

Perrimon³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

202

285

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“…may have a causal link to gastric carcinogenesis. 38 For example, it is previously reported that Acinetobacter lwoffii infection can induce many of the same histological changes, including atrophy and metaplasia, as gastric Helicobacter infection. 39 In the stomachs of GAS-KO or omeprazole-treated C57BL/6 wild-type mice under conventional housing, chronic gastritis due to bacterial overgrowth was observed and attributed to hypochlorhydria, and then antibiotic treatment successfully resolved the gastric inflammation in these mice.…”

Section: Discussionmentioning

confidence: 99%

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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The role of viral and bacterial pathogens in gastrointestinal cancer

Cited by 43 publications

References 207 publications

The cytomegalovirus-encoded chemokine receptor US28 promotes intestinal neoplasia in transgenic mice

The cytomegalovirus-encoded chemokine receptor US28 promotes intestinal neoplasia in transgenic mice

Synergy between bacterial infection and genetic predisposition in intestinal dysplasia

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

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