Epithelial mesenchymal transition and hedgehog signaling activation are associated with chemoresistance and invasion of hepatoma subpopulations

Background & Aims: Our previous studies showed that CD133, EpCAM, and aldehyde dehydrogenase (ALDH) are useful markers to identify cancer stem cells (CSCs) in hepatocellular carcinoma (HCC) tissues. The present study aims to evaluate chemosensitivity and invasion capability of HCC based on CSC marker profiles, and to explore the underlying molecular mechanisms. Methods: Hepatoma cell lines were separated into subpopulations according to CD133, EpCAM, and ALDH expression profiles. Epithelial mesenchymal transition (EMT) and hedgehog (Hh) signaling were examined to identify their links with chemoresistance and aggressive invasion. Results: Well-differentiated cell lines were positive for CD133 + / ALDH high and CD133 + /EpCAM + at 1.5–15% and 2.3–8.3%; whereas, poorly-differentiated cells were almost all negative for these markers. FACS-enriched CD133 + /ALDH high and CD133 + /EpCAM +