Innovation of cancer treatment based on the refractory mechanism

肝细胞癌是一种侵袭性的恶性肿瘤，其主要原因是术后复发和/或转移，越来越多的证据表明，肿瘤和复发可能是由一小部分干细胞亚群，即所谓的癌症干细胞(CSCs)驱动的。PreviousinvestigationsrevealedthatgliomaandbreastCSCswerefoundtoexhibitintrinsicallylowproteasomeactivity.据报道，乳腺CSCs比相应的非致瘤细胞含有更低水平的ROS。我们观察到了两种干细胞特征，低蛋白酶体活性和低细胞内ROSinHC细胞。我们使用双色smallsubpopulationofHCCcellsdemonstratedasymmetricdivisions.TheirremarkabletumorigenicityinNOD/SCID分离具有这些干细胞特征的细胞。可视化的FAC小鼠聚集了HCCCSC的癌症启动潜能。综合基因表达分析表明，趋化因子相关基因在CSCs亚群中上调。我们鉴定的肝癌CSCs在体外促进了巨噬细胞的迁移，并在体内通过巨噬细胞的募集证明了转移的潜力。在肝细胞癌根治术后患者中，肝微环境中CSC特异性基因信号与复发有显著相关性。干细胞特性监测系统是分析CSCs微环境在人肝细胞癌中的活体意义的一种有前景的工具。

Hepatocellular carcinoma (HCC) is one of the aggressive malignancies mainly due to the recurrence and/or metastasisevenaftercurativeresection.Thereis emergingevidencethattumormetastasisand recurrencemight be driven by a small subpopulation of stemness cells, so-called cancer stem cells (CSCs). PreviousinvestigationsrevealedthatgliomaandbreastCSCswerefoundtoexhibitintrinsicallylowproteasomeactivity. It was reported that breast CSCs contained lower level of reactive oxygen species (ROS) than corresponding non-tumorigenic cells. We visualized two stem cell features, low proteasome activity and low intracellular ROSinHCCcells. We usedtwo-color FACSsortingtoisolatethecellswith these stemcellfeatures.Avisualized smallsubpopulationofHCCcellsdemonstratedasymmetricdivisions.TheirremarkabletumorigenicityinNOD/SCID micesuggestedthecancerinitiation potentialofthe HCCCSCs.Comprehensivegeneexpression analysisrevealedthat chemokine-related genes were upregulated in the CSCs subpopulation. Our identified HCC CSCs facilitated the migration of macrophages in vitro, and demonstrated the metastatic potentials with recruitment of macrophages in vivo. In the patients after curative operation for HCC, the CSC-specific gene signature in the liver microenvironments has a significant correlation to the recurrence. The monitoring system of the stem cell features is a promising tool to analyze the in vivo significance of CSCs microenvironments in human HCC.