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Browsing by Author "Yilmaz, Mustafa"

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    Citation - WoS: 14
    Citation - Scopus: 14
    Effect of Adipocyte-Secreted Factors on Epcam+/Cd133+hepatic Stem Cell Population
    (Academic Press Inc Elsevier Science, 2016-06) Karagonlar, Zeynep Firtina; Koc, Dogukan; Sahin, Eren; Avci, Sanem Tercan; Yilmaz, Mustafa; Atabey, Nese; Erdal, Esra
    Recent epidemiological studies have associated obesity with a variety of cancer types including HCC. However, the tumor initiating role of obesity in hepatocarcinogenesis is still unknown. The objective of this paper is to investigate the effect of adipocyte-secreted factors on EpCAM+/CD133+ cancer stern cells and to identify which factors play a role in modulating hepatic cancer stem cell behavior. Our results demonstrated that adipocyte-secreted factors affect motility and drug resistance of EpCAM+/CD133+ cells. When incubated with adipocyte conditioned media, EpCAM-F/CD133+ cells exhibited augmented motility and reduced sorafenib-induced apoptosis. Using array-based system, we identified secretion of several cytokines such as IL6, IL8 and MCP1 by cultured adipocytes and activation of c-Met, STAT3 and ERK1/2 signaling pathways in EpCAM-F/CD133+ cells incubated with adipocyte conditioned media. Treating EpCAM+/CD133+ cancer stem cells with IL6 receptor blocking antibody or c-Met inhibitor SU11274 both reduced the increase in motility; however SU11274 had greater effect on relieving protection from sorafenib-induced apoptosis. These results indicate that adipocyte-secreted factors might regulate cancer stem cell behavior through several signaling molecules including c-Met, STAT3 and ERK1/2 and inhibition of these signaling pathways offer novel strategies in targeting the effect of adipose derived cytokines in cancer. (C) 2016 Elsevier Inc. All rights reserved.
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