-casein-derived peptides, produced by bacteria, stimulate cancer cell invasion and motility

Oliveira, Maria José; Damme, Jozef Van; Lauwaet, Tineke; Corte, Veerle De; Bruyne, Georges De; Verschraegen, Gerda; Vaneechoutte, Mario; Goethals, Marc; Ahmadian, Mohammad Réza; Müller, Oliver; Vandekerckhove, Joël; Mareel, Marc; Leroy, Ancy

doi:10.1093/emboj/cdg586

Cited by 19 publications

(21 citation statements)

References 94 publications

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“…Collagen Invasion Assay-Collagen invasion assays were performed as previously described (29). Briefly, collagen gels were prepared in 6-well plates (Becton and Dickinson, Bedford, MA), using a collagen type I solution (Upstate Biotechnology, Lake Placid, NY), and polymerized overnight at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Helicobacter pylori Induces Gastric Epithelial Cell Invasion in a c-Met and Type IV Secretion System-dependent Manner

Oliveira

Costa

et al. 2006

Journal of Biological Chemistry

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Helicobacter pylori interacts with gastric epithelial cells, activating signaling pathways important for carcinogenesis. In this study we examined the role of H. pylori on cell invasion and the molecular mechanisms underlying this process. The relevance of H. pylori cag pathogenicity island-encoded type IV secretion system (T4SS), CagA, and VacA for cell invasion was also investigated. We found that H. pylori induces AGS cell invasion in collagen type I and in Matrigel invasion assays. H. pyloriinduced cell invasion requires the direct contact between bacteria and cancer cells. H. pylori-mediated cell invasion was dependent on the activation of the c-Met receptor and on increased MMP-2 and MMP-9 activity. The abrogation of the c-Met receptor using the specific NK4 inhibitor or the silencing of c-Met expression with small interference RNA suppressed both cell invasion and MMP activity. Studies with different H. pylori strains revealed that cell invasion, c-Met tyrosine phosphorylation, and increased MMP-2 and MMP-9 activity were all dependent on the presence of a functional bacterial T4SS, but not on VacA cytotoxicity. Our findings demonstrate that H. pylori strains with a functional T4SS stimulate gastric epithelial cell invasion through a c-Met-dependent signaling pathway that comprises an increase in MMP-2 and MMP-9 activity.Helicobacter pylori is a bacterial pathogen that colonizes the gastric mucosa of more than half of the human population (1). In most individuals the infection induces chronic superficial gastritis, a condition that will remain throughout life. However, in some individuals, more severe outcomes of the infection may develop, such as peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma, and gastric carcinoma (2). This diversity of clinical outcomes associated with H. pylori infection is probably a result of the interactions among host, environmental, and bacterial virulence factors (2, 3). Numerous studies have shown that H. pylori is able to interact with gastric epithelial cells, activating signaling pathways, modifying host cellular functions, and inducing cell phenotypes important for carcinogenesis (4 -7). One of the less explored cell phenotypes induced by H. pylori is cellular invasion. Although little is known about the mechanisms involved in this process, H. pylori was shown to activate tyrosine kinase receptors frequently involved in invasion-related pathways, such as the epidermal growth factor receptor (EGFR), 4 Her2/Neu (ErbB-2), and c-Met (8 -10).Another group of molecules associated with cancer cell invasion and influenced by H. pylori are matrix metalloproteinases (MMPs) (11). MMP expression and activity are frequently enhanced in tumors as compared with normal tissue (11,12). It has been shown that H. pylori up-regulates the expression and activity of several MMPs, both in gastric epithelial cell lines and in the gastric mucosa (13-15).H. pylori virulence factors differentially interfere with signaling pathways in gastric epithelial cells (16). One well establishe...

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Section: Methodsmentioning

confidence: 99%

Helicobacter pylori Induces Gastric Epithelial Cell Invasion in a c-Met and Type IV Secretion System-dependent Manner

Oliveira

Costa

et al. 2006

Journal of Biological Chemistry

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“…The conditioned medium was analysed for proteinases activity using gelatin and b-casein zymography (gels loaded with 12 and 100 mg of protein, respectively) as described earlier (Oliveira et al, 2003). Quantification of band density was done using the Quantity One software (version 4.0, Bio-Rad, Hercules, CA, USA), unless specified.…”

Section: Gelatin and B-casein Zymographymentioning

confidence: 99%

Extracellular cleavage and shedding of P-cadherin: a mechanism underlying the invasive behaviour of breast cancer cells

et al. 2009

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Cell-cell adhesion is an elementary process in normal epithelial cellular architecture. Several studies have shown the role mediated by cadherins in this process, besides their role in the maintenance of cell polarity, differentiation and cell growth. However, during tumour progression, these molecules are frequently altered. In breast cancer, tumours that overexpress P-cadherin usually present a high histological grade, show decreased cell polarity and are associated with worse patient survival. However, little is known about how this protein dictates the very aggressive behaviour of these tumours. To achieve this goal, we set up two breast cancer cell models, where P-cadherin expression was differently modulated and analysed in terms of cell invasion, motility and migration. We show that P-cadherin overexpression, in breast cancer cells with wild-type E-cadherin, promotes cell invasion, motility and migration. Moreover, we found that the overexpression of P-cadherin induces the secretion of matrix metalloproteases, specifically MMP-1 and MMP-2, which then lead to P-cadherin ectodomain cleavage. Further, we showed that soluble P-cadherin fragment is able to induce in vitro invasion of breast cancer cells. Overall, our results contribute to elucidate the mechanism underlying the invasive behaviour of P-cadherin expressing breast tumours.

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“…colon cancer cells via a 13mer casein-derived peptide involving Cdc42 and inactivation of RhoA and PI3 kinase, again suggesting that enteric bacteria may promote tumour progression (Oliveira 2003). Human herpes virus 8 and HIV-1 are implicated in haemangiomas and Kaposi's sarcoma.…”

Section: Induction Of Invasion and Angiogenesis: Molecular Triggersmentioning

confidence: 99%

Parallels in invasion and angiogenesis provide pivotal points for therapeutic intervention

Eccles¹

2004

Int. J. Dev. Biol.

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Biological evolution is economical and successful fundamental processes are frequently recapitulated. There are remarkable similarities in the molecular mechanisms which enable tumour cells to invade into surrounding tissues and activated endothelial cells to generate new capillaries, which facilitate the growth and dissemination of cancer. Indeed these pathological processes are themselves based upon key vertebrate developmental processes, and in some cases parallel strategies used by microorganisms to colonise their hosts' tissues. The aim of this review is to explore these parallels in more detail and indicate possible pivotal points for therapeutic intervention. These novel approaches may ultimately optimise the selective targeting of processes involved in tumour invasion and angiogenesis, while sparing normal adult proliferating tissues. Strategies include inhibition of oncogenic pathways in tumour cells which not only stimulate tumour cell growth and invasion, but also initiate neoangiogenesis by upregulation of angiogenic cytokines. Secondly, downstream signalling pathways, transcriptional regulation and effectors common to both processes, and finally points of interaction/cross-talk between tumour cells and endothelial cells which are necessary to enable invasion and angiogenesis to proceed. +44-20-8722-4134. e-mail: sue.eccles@icr.ac.uk Abbreviations used in this paper: ADAM, adamalysin related membrane protease; APC, adenomatous polyposis coli; BM, basement membrane; BTC, betacellulin; COX-2, cyclo-oxygenase 2; FAK, focal adhesion kinase; FAP, familial adenomatous polyposis; FGF(R), fibroblast growth factor (receptor); GSK3, glycogen synthase kinase 3; HGF, hepatocyte growth factor; HIF, hypoxia inducible factor; HRG, heregulin; IL, interleukin; ILK, integrin linked kinase; iNOS, inducible nitric oxide synthase; MAPK, mitogen activated kinase; MIF, migration inhibitory factor; MMP, matrix metalloprotease; NSAID, non-steroidal anti-inflammatory drug; OPN, osteopontin; PAI-1, plasminogen activator inhibitor; PGE, prostaglandin E; PI3K, phosphatidylinositol 3 kinase; PTEN, phosphatase and tensin homologue; RTK, receptor tyrosine kinase; TGFα(β) (R), transforming growth factor α(β)(receptor); uPA(R), urokinase plasminogen activator (receptor); VEGF, vascular endothelial growth factor; VHL, von Hippel Lindau. KEY WORDS: motility, proteolysis, signalling, angiogenesis, invasion Parallels in invasion and angiogenesisTaking a reductionist approach, we can consider that both tumour invasion and capillary sprouting require that cells successfully manage the following challenges: survival in ectopic environments where normal anti-apoptotic signals may be lacking; overcoming the "default" position of quiescence in adult differentiated cells (G 0 ) and activation of proliferation; modification of adhesive interactions with the extracellular matrix and surrounding cells enabling tissue plasticity; acquisition of migratory capacity and ability to respond to chemokine gradients and other soluble or immob...

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-casein-derived peptides, produced by bacteria, stimulate cancer cell invasion and motility

Cited by 19 publications

References 94 publications

Helicobacter pylori Induces Gastric Epithelial Cell Invasion in a c-Met and Type IV Secretion System-dependent Manner

Helicobacter pylori Induces Gastric Epithelial Cell Invasion in a c-Met and Type IV Secretion System-dependent Manner

Extracellular cleavage and shedding of P-cadherin: a mechanism underlying the invasive behaviour of breast cancer cells

Parallels in invasion and angiogenesis provide pivotal points for therapeutic intervention

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