Monzani Elena, Facchetti Floriana, Galmozzi Enrico, Corsini Elena, Benetti Anna, Cavazzin Chiara, Gritti Angela, Piccinini Andrea, Porro Danilo, Santinami Mario, Invernici Gloria, Parati Eugenio, Alessandri Giulio, La Porta Caterina A M
Department of Biomolecular Science and Biotechnology, University of Milan, Milan, Italy.
Eur J Cancer. 2007 Mar;43(5):935-46. doi: 10.1016/j.ejca.2007.01.017. Epub 2007 Feb 22.
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 transdifferentiate 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.
大多数癌症尤其是黑色素瘤难以根除，可能根本原因在于对靶点的错误识别。肿瘤群体中具有肿瘤形成关键作用的癌症干细胞/起始细胞的鉴定，可能会开启新的药理学前景。我们的数据显示了人类黑色素瘤的三个主要新发现：首先，黑色素瘤活检样本中含有一部分表达CD133的细胞（CD133+），后者能够在NOD-SCID小鼠体内形成Mart-1阳性肿瘤。其次，已发现人类黑色素瘤细胞系WM115同时表达CD133和ABCG2标志物。该细胞系以悬浮球体形式生长，表达典型的祖细胞和成熟神经元/少突胶质细胞标志物，并且在特定生长条件下能够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，该细胞系产生的异种移植物中CD133和ABCG2水平较低。第三，WM115细胞表达最重要的血管生成和淋巴管生成因子，如Notch 4、Prox1和血小板反应蛋白，它们可协同促进黑色素瘤在体内的致瘤能力发展。因此，在本研究中，我们证明了黑色素瘤活检样本以及体外培养和异种移植中建立的黑色素瘤细胞系中均存在干细胞/起始亚群。有趣的是，鉴于黑色素瘤主要通过淋巴管发生转移，在此我们证明了一种黑色素瘤细胞系表达典型的淋巴管生成因子。
