Data from DLK1 as a Potential Target against Cancer Stem/Progenitor Cells of Hepatocellular Carcinoma

Abstract

<div>Abstract<p>Delta-like 1 homolog (DLK1; <i>Drosophila</i>) is a hepatic stem/progenitor cell marker in fetal livers that plays a vital role in oncogenesis of hepatocellular carcinoma (HCC). The aim of this study is to investigate whether DLK1 could serve as a potential therapeutic target against cancer stem/progenitor cells of HCC. DLK1<sup>+</sup> and DLK1<sup>−</sup> cells were sorted by fluorescence-activated cell sorting and magnetic-activated cell sorting, respectively, and then were evaluated by flow cytometry. The biological behaviors of these isolated cells and those with <i>DLK1</i> knockdown were assessed by growth curve, colony formation assay, spheroid colony formation, chemoresistance, and <i>in vivo</i> tumorigenicity. Adenovirus-mediated RNA interference was used to knockdown the endogenous <i>DLK1</i>. We found that DLK1<sup>+</sup> population was less than 10% in almost all 17 HCC cell lines examined. DLK1<sup>+</sup> HCC cells showed stronger ability of chemoresistance, colony formation, spheroid colony formation, and <i>in vivo</i> tumorigenicity compared with DLK1<sup>−</sup> cells. The DLK1<sup>+</sup> HCC cells could generate the progeny without DLK1 expression. Furthermore, <i>DLK1</i> knockdown could suppress the ability of proliferation, colony formation, spheroid colony formation, and <i>in vivo</i> tumorigenicity of Hep3B and Huh-7 HCC cells. Our data suggested that DLK1<sup>+</sup> HCC cells have characteristics similar to those of cancer stem/progenitor cells. RNA interference against <i>DLK1</i> can suppress the malignant behaviors of HCC cells, possibly through directly disrupting cancer stem/progenitor cells, which suggested that DLK1 could be a potential therapeutic target against the HCC stem/progenitor cells. <i>Mol Cancer Ther; 11(3); 629–38. ©2012 AACR</i>.</p></div>