The cancer stem cell theory states that a subset of tumor cells, termed cancer stem cells (CSCs), has the ability to self‐renew and differentiate within the tumors. According to this theory, CSCs would be mainly responsible for tumor initiation, progression, resistance to therapy, recurrence, and metastasis. In this study, a culture system was setup to enrich CSCs from bladder cancer (T24), lung cancer (A549), colorectal cancer (CaCo‐2), and osteosarcoma (MG63) cell lines, through sphere formation. Magnetic‐activated cell sorting was also used to further increase CSC enrichment. Subsequently, molecular characterization of CSC‐enriched cell populations and parental cells was carried out, by exploring the expression levels of stem markers and the enzyme nicotinamide N‐methyltransferase (NNMT). Results obtained showed a significant upregulation of stem cell markers in CSC‐enriched populations, obtained upon sphere formation, compared with parental counterparts. Moreover, NNMT expression levels were markedly increased in samples enriched with CSCs with respect to control cells. Considering the fundamental role played by CSCs in carcinogenesis, reported data strengthen the hypothesis that sustains a pivotal role of NNMT in cancer growth and metastasis. In addition, these findings could represent an important achievement for the development of new and effective anticancer therapies, based on CSC‐associated targets.

中文翻译：

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癌症干细胞富集与烟酰胺 N-甲基转移酶表达增强有关

癌症干细胞理论指出，肿瘤细胞的一个子集，称为癌症干细胞 (CSC)，具有在肿瘤内自我更新和分化的能力。根据这一理论，CSCs 将主要负责肿瘤的发生、进展、对治疗的抵抗、复发和转移。在这项研究中，建立了一个培养系统，通过球体形成来富集来自膀胱癌 (T24)、肺癌 (A549)、结直肠癌 (CaCo-2) 和骨肉瘤 (MG63) 细胞系的 CSC。磁激活细胞分选也用于进一步增加 CSC 富集。随后，通过探索干标记和烟酰胺 N-甲基转移酶 (NNMT) 的表达水平，对 CSC 富集的细胞群和亲本细胞进行了分子表征。获得的结果表明，与亲本对应物相比，在球体形成时获得的富含 CSC 的群体中的干细胞标志物显着上调。此外，相对于对照细胞，在富含 CSC 的样品中 NNMT 表达水平显着增加。考虑到 CSCs 在致癌作用中发挥的基本作用，报告的数据加强了 NNMT 在癌症生长和转移中发挥关键作用的假设。此外，这些发现可能代表了基于 CSC 相关目标开发新的有效抗癌疗法的重要成就。考虑到 CSCs 在致癌作用中发挥的基本作用，报告的数据加强了 NNMT 在癌症生长和转移中发挥关键作用的假设。此外，这些发现可能代表了基于 CSC 相关靶点开发新的有效抗癌疗法的重要成就。考虑到 CSCs 在致癌作用中发挥的基本作用，报告的数据加强了 NNMT 在癌症生长和转移中发挥关键作用的假设。此外，这些发现可能代表了基于 CSC 相关靶点开发新的有效抗癌疗法的重要成就。