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Inflammation mobilizes tumor cells
Date:3/19/2014

Researchers of Ludwig-Maximilians-Universitaet (LMU) in Munich have discovered a novel feedback mechanism that provides a mechanistic link between chronic inflammation and carcinogenesis.

Malignant tumors pose a major threat to survival largely because they shed mobile cells that can form secondary tumors in other tissues. This process requires a fundamental change in the character of cells within the primary tumor, insofar as members of a localized cell mass must be converted into actively migrating cells that invade into the surrounding tissue and blood vessels, and finally settle in distant tissues. A growing body of evidence suggests that inflammatory reactions promote such cellular transformation. The protein interleukin 6 (IL-6) is known to a play a significant role in inflammatory signalling. IL-6 is a cytokine, a signal molecule that is produced and secreted both by immune cells and by tumor cells and binds specifically to a receptor (IL-6R) that is found on the surfaces of many cell types. "As we have now shown, even brief exposure to IL-6 can lead to long-lasting alterations in colon cancer cells that enhance their mobility and thus increase their metastasizing potential," says Heiko Hermeking of LMU's Institute of Pathology.

Short RNA strands repress metastasis

Hermeking and his colleagues set out to discover the functional basis for this effect of IL-6. Using cell cultures derived from colon carcinomas, they found that IL-6 is part of a feedback loop, which also includes a short RNA, microRNA-34a (miR-34a). It turns out that miR-34a plays a central role in repressing the production of tumor-promoting proteins, and thereby normally serves to inhibit tumorigenesis and metastasis. But as Hermeking explains, "Activation of IL-6R upon binding of IL-6 essentially disables this inhibitory mechanism. It does so by activating the transcription factor STAT3, which in turn inhibits expression of the miR-34a gene by
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Contact: Luise Dirscherl
dirscherl@lmu.de
49-892-180-2706
Ludwig-Maximilians-Universitt Mnchen
Source:Eurekalert

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