Melanoma contains CD133 and ABCG2 positive cells with enhanced tumourigenic potential

Melanoma contains CD133 and ABCG2 positive cells with enhanced tumourigenic potential
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DOI:
10.1016/j.ejca.2007.01.017
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发表时间:
2007-03-01
影响因子:
8.4
通讯作者:
La Porta, Caterina A. M.
La Porta, Caterina A. M.
中科院分区:
医学1区
文献类型:
--
作者:
Monzani, Elena;Facchetti, Floriana;La Porta, Caterina A. M.

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未能根除大多数癌症,特别是黑色素瘤,可能与错误识别目标一样根本。肿瘤群体中对肿瘤形成起关键作用的癌症干/起始细胞的鉴定可能会开辟新的药理学视角。我们的数据显示了人类黑色素瘤的三个主要新颖之处:首先,黑色素瘤活检包含表达 CD133 (CD133+) 的细胞子集,后者能够在 NOD-SCID 小鼠中形成 Mart-1 阳性肿瘤。其次,WM115(一种人类黑色素瘤细胞系)被发现表达 CD133 和 ABCG2 标记物。该细胞系生长为漂浮球体,表达典型的祖细胞和成熟的神经元/少突胶质细胞标记物,并且能够在特定的生长条件下转分化为星形胶质细胞或间充质谱系。与用 CD133+ 活检黑色素瘤细胞生成的异种移植物一样,由该细胞系生成的异种移植物显示出较低水平的 CD133 和 ABCG2。第三,WM115细胞表达最重要的血管生成和淋巴管生成因子,例如notch 4、prox1和podoplanin,它们可以在体内黑色素瘤的致瘤能力的发展中发挥作用。因此,在这项研究中,我们在活检和体外培养的已建立的黑色素瘤细胞系中证明了黑色素瘤中干细胞/起始亚群的存在。 异种移植物。有趣的是,考虑到黑色素瘤主要通过淋巴管进行转移,本文中我们证明黑色素瘤细胞系表达典型的淋巴管生成因子。 (c) 2007 Elsevier Ltd. 保留所有权利。
The failure to eradicate most cancers and in particular melanoma may be as fundamental as a misidentification of the target. The identification of cancer stem/initiating cells within the tumour population with a crucial role for tumour formation may open new pharmacological perspectives. Our data show three main novelties for human melanoma: firstly, melanoma biopsy contains a subset of cells expressing CD133 (CD133+) and the latter is able to develop a Mart-1 positive tumour in NOD-SCID mice. Secondly, the WM115, a human melanoma cell line, has been found to express both CD133 and ABCG2 markers. This cell line grows as floating spheroids, expresses typical progenitors and mature neuronal/oligodendrocyte markers and is able to trans differentiate into astrocytes or mesenchymal lineages under specific growth conditions. As in xenografts generated with CD133+ biopsy melanoma cells, those produced by the cell line displayed lower levels of CD133 and ABCG2. Thirdly, the WM115 cells express the most important angiogenic and lymphoangiogenic factors such as notch 4, prox1 and podoplanin which can cooperate in the development of the tumourigenic capability of melanoma in vivo.Therefore, in this study, we demonstrate the presence of stem/initiating subsets in melanoma both in biopsy and in an established melanoma cell line grown in vitro and in xenografts. interestingly, considering that melanoma gives metastasis primarily through lymphatic vessels, herein, we demonstrated that a melanoma cell line expresses typical lymphoangiogenic factors. (c) 2007 Elsevier Ltd. All rights reserved.