Alpha-6 integrin is necessary for the tumourigenicity of a stem cell-like subpopulation within the MCF7 breast cancer cell line
Alpha-6 integrin is necessary for the tumourigenicity of a stem cell-like subpopulation within the MCF7 breast cancer cell line
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DOI：
10.1002/ijc.23103
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发表时间：
2008-01-15
影响因子：
6.4
通讯作者：
Purushotham, Anand D.
中科院分区：
文献类型：
--
作者：
Cariati, Massimiliano;Naderi, Ali;Purushotham, Anand D.
乳腺上皮干细胞的鉴定提出了这样的假设，即这些细胞可能在乳腺癌的发病机制中至关重要。为了进一步支持这一点，最近在原发性和转移性乳腺癌样本中鉴定出了高度致瘤性的癌细胞亚群。在这项研究中，在乳腺癌细胞系MCF-7中鉴定出了一个细胞亚群，该亚群显示出通常归因于干细胞的特征。该亚群能够在锚定非依赖性条件下生长为球形类器官，显示出对促凋亡剂的抗性，并且比其亲本系具有显著更大的致瘤性，其中少至1，000个细胞能够在免疫缺陷小鼠中形成肿瘤。该亚群内的细胞可以通过连续传代以锚定独立性富集，并且特征在于粘附分子α 6-整联蛋白的过表达。α-6整联蛋白被证明是这些细胞的生长和存活所必需的，因为ITGA 6的敲低导致乳腺球衍生的细胞失去其作为乳腺球生长的能力并消除其在小鼠中的致瘤性。这些发现支持在乳腺癌细胞中存在高度致瘤性亚群。此外，它显示α 6-整联蛋白作为针对乳腺癌细胞的肿瘤生成亚群的潜在治疗靶点。(C)2007 Wiley-Liss，Inc.
The identification of mammary epithelial stem cells raises the hypothesis that these cells may be crucial in the pathogenesis of breast cancer. To further support this, a highly tumourigenic sub-population of cancer cells has recently been identified in primary and metastatic breast cancer samples. In this study, a sub-population of cells displaying features normally attributed to stem cells was identified within the breast cancer cell line MCF-7. This sub-population is capable of growth in anchorage-independent conditions as spherical organoids, displays resistance to proapoptotic agents and significantly greater tumourigenicity than its parental line, with as few as 1,000 cells able to form tumours in immunodeficient mice. Cells within this sub-population can be enriched by serial passages in anchorage-independence, and are characterized by over-expression of the adhesion molecule alpha 6-integrin. Alpha-6 integrin proves to be required for the growth and survival of these cells, as the knockdown of ITGA6 causes mammosphere-derived cells to lose their ability to grow as mammospheres and abrogates their tumourigenicity in mice. These findings support the existence of a highly tumourigenic sub-population in breast cancer cells. Furthermore, it shows alpha 6-integrin as a potential therapeutic target aimed at tumour-generating subsets of breast cancer cells. (C) 2007 Wiley-Liss, Inc.