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Cell Communication and Signaling 2008, 6:2<br />

http://www.biosignaling.com/content/6/1/2<br />

lished that FAs exist in vivo, mediating cell-matrix junctions<br />

at the basolateral surface of polarized cells [57]. The<br />

fact that CagA injection requires integrin activation leads<br />

to the question of whether H. <strong>pylori</strong> can contact FAs at the<br />

basolateral membrane in vivo. Several studies have shown<br />

that CagA is necessary for the disruption of the intercellular<br />

tight junctions of polarized cells [58-60]. Furthermore,<br />

it has been demonstrated that injected CagA preferentially<br />

localizes to the apical membrane of T84 cells [61].<br />

Detailed models have been proposed in recent reviews<br />

[11,62], suggesting that moderate amounts of CagA might<br />

be injected across the apical membrane without the need<br />

of integrins in early phases of infection. Together with<br />

other secreted bacterial and/or <strong>host</strong> factors (e.g. soluble H.<br />

<strong>pylori</strong> factors or cellular matrix metalloproteases), injected<br />

CagA then supports the disruption of intercellular <strong>adhesions</strong><br />

[25,63,64] allowing H. <strong>pylori</strong> to enter the intercellular<br />

space. In fact, in biopsies from patients with intestinal<br />

metaplasia and gastric cancer, H. <strong>pylori</strong> was found in the<br />

intercellular space and lamina propria [65], indicating<br />

that H. <strong>pylori</strong> has access to FAs at later time points of infection<br />

in vivo. Consequently, it is important to analyze the<br />

consequences of CagA injection and FA deregulation in<br />

vivo. CagA PY -associated cell elongation possibly hinders<br />

H. <strong>pylori</strong>-mediated cell migration, since failure of tail<br />

retraction might result in a reduced migration speed. In<br />

contrast, elongation allows cells to pass tissues more easily,<br />

which would support invasive growth of single cells.<br />

Therefore, analyzing the consequences of cell elongation<br />

and migration in vivo should lead to novel insights into H.<br />

<strong>pylori</strong> pathogenesis.<br />

Competing interests<br />

The authors declare that they have no competing interests.<br />

Authors' contributions<br />

SS and SW drafted and wrote the manuscript. CW participated<br />

in the design of the manuscript and prepared the<br />

figures. All authors read and approved the final manuscript.<br />

Acknowledgements<br />

We thank Catherine Haynes for critical reading of the manuscript. The<br />

work is supported by the Deutsche Forschungsgemeinschaft (We2843/2-<br />

1).<br />

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