Wayne State University, Karmanos Cancer Institute, Department of Pathology, Detroit, MI, USA.
Expert Opin Ther Targets. 2012 Oct;16(10):1041-54. doi: 10.1517/14728222.2012.714774. Epub 2012 Aug 9.
Mesenchymal stem cells (MSCs) are one subgroup of adult stem cells and possess a proliferative potential and ability to differentiate into various ceells.
Emerging evidence suggests that MSCs can reprogram toward cancer stem cells (CSCs), due to alterations of intrinsic and extrinsic microenvironments, leading to tumorigenesis. The CSC concept has fundamental clinical implications because of its involvement in cell migration/invasion, metastasis, and treatment resistance. Therefore, targeting CSCs provides a novel therapeutic strategy for cancer treatment. However, the origin of CSCs and its molecular connections are not fully understood. Emerging evidence suggests the existence of an inter-relationship between CSCs and epithelial-to-mesenchymal transition (EMT) phenotypic cells, in the context of inflammation and hypoxia, as well as the potential role of miRNAs.
We suggest that targeting CSC signatures along with EMT, inflammation, and hypoxia will provide a more effective therapeutic approach for the elimination of CSCs. To that end, curcumin especially its synthetic novel analog CDF have been shown to attenuate CSC characteristics along with the deregulation of multiple pathways and miRNAs, leading to the inhibition of human tumor growth in vivo, suggesting the potential role of CDF as an anti-tumor agent for the prevention/treatment of tumor progression.
间充质干细胞(MSCs)是成体干细胞的一个亚群,具有增殖潜力和分化为多种细胞的能力。
新出现的证据表明,由于内在和外在微环境的改变,MSCs 可以向癌症干细胞(CSC)重编程,从而导致肿瘤发生。CSC 概念具有重要的临床意义,因为它涉及细胞迁移/侵袭、转移和治疗耐药性。因此,针对 CSCs 提供了一种治疗癌症的新策略。然而,CSC 的起源及其分子联系尚不完全清楚。新出现的证据表明,在炎症和缺氧的情况下,CSC 与上皮-间充质转化(EMT)表型细胞之间存在相互关系,以及 miRNA 的潜在作用。
我们建议,针对 CSC 特征以及 EMT、炎症和缺氧,将提供一种更有效的治疗方法,以消除 CSCs。为此,姜黄素,特别是其合成的新型类似物 CDF,已被证明可以减弱 CSC 的特征,同时调节多种途径和 miRNA,从而抑制体内人肿瘤的生长,表明 CDF 作为一种抗肿瘤药物在预防/治疗肿瘤进展方面具有潜在作用。