Department of Surgery, Far Eastern Memorial Hospital, New Taipei City 22060, Taiwan.
Department of Hepato Gastroenterology, Linkou Medical Center, Chang-Gung University, Taoyuan City 33305, Taiwan.
Int J Mol Sci. 2023 Jan 11;24(2):1417. doi: 10.3390/ijms24021417.
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death globally. The cancer stem cells (CSCs) of HCC are responsible for tumor growth, invasion, metastasis, recurrence, chemoresistance, target therapy resistance and radioresistance. The reported main surface markers used to identify liver CSCs include epithelial cell adhesion/activating molecule (EpCAM), cluster differentiation 90 (CD90), CD44 and CD133. The main molecular signaling pathways include the Wnt/β-catenin, transforming growth factors-β (TGF-β), sonic hedgehog (SHH), PI3K/Akt/mTOR and Notch. Patients with EpCAM-positive alpha-fetoprotein (AFP)-positive HCC are usually young but have advanced tumor-node-metastasis (TNM) stages. CD90-positive HCCs are usually poorly differentiated with worse prognosis. Those with CD44-positive HCC cells develop early metastases. Those with CD133 expression have a higher recurrence rate and a shorter overall survival. The Wnt/β-catenin signaling pathway triggers angiogenesis, tumor infiltration and metastasis through the enhancement of angiogenic factors. All CD133+ liver CSCs, CD133+/EpCAM+ liver CSCs and CD44+ liver CSCs contribute to sorafenib resistance. SHH signaling could protect HCC cells against ionizing radiation in an autocrine manner. Reducing the CSC population of HCC is crucial for the improvement of the therapy of advanced HCC. However, targeting CSCs of HCC is still challenging.
肝细胞癌 (HCC) 是全球癌症死亡的主要原因之一。HCC 的癌症干细胞 (CSC) 负责肿瘤的生长、侵袭、转移、复发、化疗耐药、靶向治疗耐药和放疗耐药。已报道的用于鉴定肝 CSC 的主要表面标志物包括上皮细胞黏附/激活分子 (EpCAM)、分化簇 90 (CD90)、CD44 和 CD133。主要的分子信号通路包括 Wnt/β-catenin、转化生长因子-β (TGF-β)、 sonic hedgehog (SHH)、PI3K/Akt/mTOR 和 Notch。EpCAM 阳性、α-胎蛋白 (AFP) 阳性 HCC 患者通常年轻，但肿瘤-淋巴结-转移 (TNM) 分期较晚。CD90 阳性 HCC 通常分化较差，预后较差。CD44 阳性 HCC 细胞较早发生转移。CD133 表达的患者复发率较高，总生存期较短。Wnt/β-catenin 信号通路通过增强血管生成因子触发血管生成、肿瘤浸润和转移。所有 CD133+肝 CSC、CD133+/EpCAM+肝 CSC 和 CD44+肝 CSC 均导致索拉非尼耐药。SHH 信号以自分泌的方式保护 HCC 细胞免受电离辐射。减少 HCC 的 CSC 群体对于改善晚期 HCC 的治疗至关重要。然而，针对 HCC 的 CSC 仍然具有挑战性。
