Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China ; Department of Hepatobiliary Surgery, Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu 210008, China.
Gastroenterol Res Pract. 2013;2013:782581. doi: 10.1155/2013/782581. Epub 2013 Sep 30.
Background. Despite improvement in treatment, the prognosis of hepatocellular carcinoma (HCC) remains disastrous. Cancer stem cells (CSCs) may be responsible for cancer malignant behaviors. ATP-binding cassette, subfamily G, member 2 (ABCG2) is widely expressed in both normal and cancer stem cells and may play an important role in cancer malignant behaviors. Methods. The expression of ABCG2 in HCC tissues and SMMC-7721 cells was examined, and the relevance of ABCG2 expression with clinical characteristics was analyzed. ABCG2+ and ABCG2- cells were sorted, and the potential of tumorigenicity was determined. Expression level of ABCG2 was manipulated by RNA interference and overexpression. Malignant behaviors including proliferation, drug resistance, migration, and invasion were studied in vitro. Results. Expression of ABCG2 was found in a minor group of cells in HCC tissues and cell lines. ABCG2 expression showed tendencies of association with unfavorable prognosis factors. ABCG2 positive cells showed a superior tumorigenicity. Upregulation of ABCG2 enhanced the capacity of proliferation, doxorubicin resistance, migration, and invasion potential, while downregulation of ABCG2 significantly decreased these malignant behaviors. Conclusion. Our results indicate that ABCG2 is a potential CSC marker for HCC. Its expression level has a close relationship with tumorigenicity, proliferation, drug resistance, and metastasis ability.
尽管治疗有所改善,但肝细胞癌(HCC)的预后仍然很差。癌症干细胞(CSC)可能是导致癌症恶性行为的原因。三磷酸腺苷结合盒,G 超家族成员 2(ABCG2)在正常和癌症干细胞中广泛表达,可能在癌症恶性行为中发挥重要作用。
检测 HCC 组织和 SMMC-7721 细胞中 ABCG2 的表达,并分析 ABCG2 表达与临床特征的相关性。对 ABCG2+和 ABCG2-细胞进行分选,并确定其成瘤能力。通过 RNA 干扰和过表达操纵 ABCG2 的表达水平。在体外研究增殖、耐药性、迁移和侵袭等恶性行为。
在 HCC 组织和细胞系中发现 ABCG2 在一小部分细胞中表达。ABCG2 表达与预后不良因素有一定的关联趋势。ABCG2 阳性细胞具有更高的成瘤能力。上调 ABCG2 增强了增殖、阿霉素耐药、迁移和侵袭潜能,而下调 ABCG2 则显著降低了这些恶性行为。
我们的结果表明,ABCG2 是 HCC 的潜在 CSC 标志物。其表达水平与肿瘤发生、增殖、耐药性和转移能力密切相关。