Abstract
BackgroundResistin, adipocyte-secreting adipokine, may play critical role in modulating cancer pathogenesis. The aim of this study was to investigate the effects of resistin on HCC adhesion to the endothelium, and the mechanism underlying these resistin effects.MethodsHuman SK-Hep1 cells were used to study the effect of resistin on intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expressions as well as NF-κB activation, and hence cell adhesion to human umbilical vein endothelial cells (HUVECs). 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR), an AMP-activated protein kinase (AMPK) activator, was used to determine the regulatory role of AMPK on HCC adhesion to the endothelium in regard to the resistin effects.ResultsTreatment with resistin increased the adhesion of SK-Hep1 cells to HUVECs and concomitantly induced NF-κB activation, as well as ICAM-1 and VCAM-1 expressions in SK-Hep1 cells. Using specific blocking antibodies and siRNAs, we found that resistin-induced SK-Hep1 cell adhesion to HUVECs was through NF-κB-regulated ICAM-1 and VCAM-1 expressions. Moreover, treatment with AICAR demonstrated that AMPK activation in SK-Hep1 cells significantly attenuates the resistin effect on SK-Hep1 cell adhesion to HUVECs.ConclusionsThese results clarify the role of resistin in inducing HCC adhesion to the endothelium and demonstrate the inhibitory effect of AMPK activation under the resistin stimulation. Our findings provide a notion that resistin play an important role to promote HCC metastasis and implicate AMPK may be a therapeutic target to against HCC metastasis.
Highlights
Resistin, adipocyte-secreting adipokine, may play critical role in modulating cancer pathogenesis
Resistin induced the adhesions of SK-Hep1 cells to Human umbilical vein endothelial cells (HUVEC) In order to determine the Hepatocellular carcinoma (HCC) cancer cell adhesion to the endothelium, SK-Hep1 cells were kept as the control or treated with different concentrations of resistin (i.e. 5, 10, 25 and 50 ng/ml) for 4 h and subsequently marked with the fluorescent cell tracker DiI to test the adhesions of cells to HUVECs
We investigated whether resistin-increased adhesions of SK-Hep1 cells to HUVECs are mediated by AMPactivated protein kinase (AMPK)
Summary
Adipocyte-secreting adipokine, may play critical role in modulating cancer pathogenesis. The maintenance and promotion of cell adhesion are critical processes in cancer cell metastasis. The intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) belong to the CAM-immunoglobulin (Ig) gene superfamily of adhesion molecules. They can induce the cancer cell adhesion to the endothelium and are involved in the immune responses of tumors [14]. The interaction between ICAM-1/VCAM-1 and their respective ligand may facilitate the adhesion of cancer cells to the vascular endothelium, and subsequently aid in the promotion of metastasis. There is no detailed information about whether resistin induces ICAM-1 and VCAM-1 expressions in cancer cells, and promotes its adhesion and invasion of the endothelium
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
