Side population of a murine mantle cell lymphoma model contains tumour-initiating cells responsible for lymphoma maintenance and dissemination.

Side population of a murine mantle cell lymphoma model contains tumour-initiating cells responsible for lymphoma maintenance and dissemination.
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鼠地幔细胞淋巴瘤模型的侧种群包含负责淋巴瘤维持和传播的肿瘤发射细胞。

DOI:
10.1111/j.1582-4934.2009.00865.x
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发表时间:
2010-06
影响因子:
5.3
通讯作者:
Ford RJ
Ford RJ
中科院分区:
医学2区
文献类型:
--
作者:
Vega F;Davuluri Y;Cho-Vega JH;Singh RR;Ma S;Wang RY;Multani AS;Drakos E;Pham LV;Lee YC;Shen L;Ambrus J Jr;Medeiros LJ;Ford RJ

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b细胞非霍奇金淋巴瘤中的“癌症干细胞”或“肿瘤起始细胞”尚未得到证实,尽管一些针对其他癌症类型的研究表明,存在这样的群体,并且代表肿瘤细胞对治疗有抵抗力并参与复发。这些细胞也可能代表淋巴瘤中假定的肿瘤“起源细胞”,但很少有实质性数据支持这一说法。利用最近建立的小鼠IL-14α× c-Myc双转基因/套细胞淋巴瘤-囊胚变异体模型的细胞系,迄今为止被称为DTG细胞系,我们在侧群(SP)中发现了一个具有“肿瘤启动细胞”特征的细胞亚群。这些特征包括与非sp相比,ABCG2和BCL-2的表达更高,端粒长度更长,自我更新能力更强,体外克隆和体内致瘤能力更强。此外,体外活力研究表明,与SP部分相比,非SP淋巴瘤亚群的寿命有限。同基因移植研究表明,与sp源性肿瘤相比,非sp源性肿瘤表现出更大的坏死/凋亡和更弱的全身播散能力。总之,我们的数据支持这样的解释,即DTG SP部分含有高度能够维持肿瘤和全身传播的细胞群,并支持“肿瘤启动细胞”发生在淋巴瘤中的概念。
‘Cancer stem cells’ or ‘tumour initiating cells’ in B-cell non-Hodgkin lymphomas have not been demonstrated, although some studies focused on other cancer types suggest that such populations exist and represent tumour cells resistant to therapy and involved in relapse. These cells may also represent a putative neoplastic ‘cell of origin’ in lymphomas, but there is little substantive data to support this suggestion. Using cell lines derived from a recently established murine IL-14α× c-Myc double transgenic/mantle cell lymphoma-blastoid variant model, heretofore referred to as DTG cell lines, we identified a subset of cells within the side population (SP) with features of ‘tumour-initiating cells’. These features include higher expression of ABCG2 and BCL-2, longer telomere length, greater self-renewal ability and higher in vitro clonogenic and in vivo tumorigenic capacities compared with non-SP. In addition, in vitro viability studies demonstrated that the non-SP lymphoma subpopulation has a limited lifespan in comparison with the SP fraction. Syngenic transplant studies showed that non-SP derived tumours, in comparison to the SP-derived tumours, exhibit greater necrosis/apoptosis and less systemic dissemination capability. In conclusion, our data support the interpretation that the DTG SP fraction contains a cell population highly capable of tumour maintenance and systemic dissemination and lends support to the concept that ‘tumour-initiating cells’ occur in lymphomas.
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