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Aberrant elevated microRNA-146a in dendritic cells (DC) induced by human pancreatic cancer cell line BxPC-3-conditioned medium inhibits DC maturation and activation
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
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2012 (English)In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 29, no 4, 2814-2823 p.Article in journal (Refereed) Published
Abstract [en]

It has been shown that the function of dendritic cell (DC) is suppressed in pancreatic cancer patients; however, the detailed mechanism involved in it remains unclear. Here, we used medium conditioned by a highly metastatic human pancreatic cancer cell line BxPC-3 [BxPC-3-conditioned medium (BxCM)] to culture human CD14 + monocyte-derived DCs in vitro. Both DC differentiation and antigen presentation function were inhibited by BxCM. The microRNA-146a (miRNA-146a) expression is aberrantly up-regulated in BxCM-treated DCs. In addition, inhibition of aberrant miRNA-146a expression partly rescues the BxCM-induced defects in differentiation and function of DCs, which may be through regulation of Smad4 expression. Taken together, our findings indicate that aberrant miRNA-146a expression is one of main factors responsible for inhibition of DC maturation and antigen presentation function, and this inhibitory effect on DCs may be due to the repression of Smad4 mediated signal pathway by BxCM.

Place, publisher, year, edition, pages
2012. Vol. 29, no 4, 2814-2823 p.
Keyword [en]
Dendritic cells, microRNA-146a, Pancreatic cancer, Smad4
National Category
Natural Sciences
URN: urn:nbn:se:uu:diva-184887DOI: 10.1007/s12032-012-0175-2ISI: 000309711600074OAI: oai:DiVA.org:uu-184887DiVA: diva2:570918
Available from: 2012-11-20 Created: 2012-11-15 Last updated: 2012-11-21Bibliographically approved

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