Effect of adipocyte-secreted factors on EpCAM+/CD133+hepatic stem cell population


Karagonlar Z. F., Koc D., Sahin E., Avci S. T., YILMAZ M., Atabey N., ...More

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol.474, no.3, pp.482-490, 2016 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 474 Issue: 3
  • Publication Date: 2016
  • Doi Number: 10.1016/j.bbrc.2016.04.137
  • Journal Name: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.482-490
  • Keywords: Adipocytes, Cytokines, HCC, IL6, c-Met, STAT3, HEPATOCYTE GROWTH-FACTOR, TUMOR-INITIATING CELLS, HEPATOCELLULAR-CARCINOMA, METABOLIC SYNDROME, CANCER, INTERLEUKIN-6, OBESITY, HEPATOCARCINOGENESIS, DIFFERENTIATION, EXPRESSION
  • Dokuz Eylül University Affiliated: Yes

Abstract

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.