Abstract 2529: Expression of ABCF1 with stem cell markers CD133/GEP/beta-catenin in fetal liver and liver cancer cells

Abstract

Abstract Understanding stem cell biology in relation to cancer is of growing importance with the cancer stem cells (CSCs) notion and recurring deregulated stem cell pathways reported in cancers. ATP-binding cassette (ABC) transporter ABCB1 (also named P-glycoprotein and MDR1) has shown to be CSC marker, mediate multidrug-resistance in model systems though with controversial clinical relevance. We have systemically examined the expression profiles of ABC genes in hepatocellular carcinoma (HCC) clinical samples. ABCF1 was significantly over-expressed in HCCs compared to the adjacent non-tumor liver tissues (P<0.001) and associated with recurrence-free survival after curative partial hepatectomy (log rank, P = 0.010). Recurrences have conventionally been attributed to aggressive cancer features and, recently, CSC features, as CSCs in small load could grow to tumor bulk. We therefore further explored the significance of ABCF1 in both fetal liver and liver cancer cells in respect to stem cell signaling. Expression of ABCF1 in fetal, neonatal and adult mouse livers were examined by immunohistochemistry, western blot and flow cytometry. Consistently, elevated ABCF1 expression was demonstrated in early embryonic stages [embryonic day 13 (E13): 42.4%; E15: 24.6%] but rarely in neonates and adult livers [1.5% and 1.2%, respectively]. Also, ABCF1 co-stained with stem cell-related marker β-catenin and hepatic CSC markers CD133 and GEP in fetal hepatocytes and in HCC cells (Table 1). ABCF1 suppression by siRNA enhanced chemo-sensitivity of the HCC cells Hep3B compared to control cells on cisplatin (cell apoptosis 7.5% vs 1.7%, P<0.001) and 5-Fluorouracil (11.7% vs 4.7%, P<0.001). Subcellular fractionation analysis on HCC cells showed that ABCF1 protein was present in both the cytoplasmic and membrane fractions. The current study highlighted the functional significance of ABCF1 in liver development and liver cancer as stem cell-related molecule regulating chemo-resistance. Table 1.Co-expression of ABCF1 and hepatic stem cell markers in mouse fetal livers and HCC cellsFetal liver cells (E15)Liver cancer cells (Hep3B)ABCF1+24.6%34.5%CD133+16.3%88.8%ABCF1+ CD133+20.9%34.3%GEP+45.7%65.7%ABCF1+ GEP+24.0%29.7%β-catenin+40.6%20.9%ABCF1+ β-catenin+13.5%17.5% Citation Format: Sze Wai Fung, Phyllis Fung Yi Cheung, Chi Wai Yip, George Sai Wah Tsao, Siu Tim Cheung. Expression of ABCF1 with stem cell markers CD133/GEP/beta-catenin in fetal liver and liver cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2529.