Hepatocellular Carcinoma with Progenitor Cell Features: High Expression of Invasion and Epithelial Mesenchymal Transition-Associated Genes
J-E Lee, B-K Oh, J Choi, S-M Yoon, T-H Um, YN Park. Yonsei University College of Medicine, Seoul, Republic of Korea
Background: Recently, it has been reported that hepatocellular carcinomas (HCCs) with progenitor cell features have more aggressive biological behavior in both in vivo and in vitro studies.
Design: We investigated expression levels of the following genes in 44 HCCs by real-time reverse transcriptase (RT)-polymerase chain reaction (PCR) or immunohistochemistry: Progenitor cell markers of cytokeratin (CK) CK19 and CD133; multidrug resistance (MDR) genes of MDR1 and MDR-associated protein (MRP) MRP1; invasion-associated genes of urokinase plasminogen activator receptor (uPAR), villin 2 (VIL2), and matrix metalloproteinase (MMP) MMP1 and MMP2; and epithelial-mesenchymal transition (EMT) regulators of Snail1 (Snail), Snail2 (Slug), Twist, and E- and N-cadherin. Correlations between expression levels of these genes and clinicopathological parameters were determined.
Results: HCCs with progenitor cell features, which showed high expression of CK19 or CD133 mRNA, revealed significantly more frequent vascular invasion compared to those without. HCCs with progenitor cell features had high mRNA levels of MRP1, uPAR, MMP1, MMP2, Snail, and Twist. Upregulation of Snail, Slug, and Twist were associated with increasing MRP1, uPAR, VIL2, and MMP2.
Conclusions: Our results suggest that HCCs with progenitor cell features have a potential for a more invasive phenotype with upregulation of invasion- and EMT- associated genes. Furthermore, elevated MRP1 expression might induce drug resistance in HCCs with progenitor cell features.
Category: Liver & Pancreas
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 169, Tuesday Morning