Metastatic-niche labelling reveals parenchymal cells with stem features
Metastatic-niche labelling reveals parenchymal cells with stem features
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DOI：
10.1038/s41586-019-1487-6
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发表时间：
2019-08-29
期刊：
影响因子：
64.8
通讯作者：
Malanchi, Ilaria
中科院分区：
文献类型：
--
作者：
Ombrato, Luigi;Nolan, Emma;Malanchi, Ilaria
直接研究周围组织内转移细胞诱导的早期细胞变化仍然是一个挑战。在这里，我们提出了一个系统，其中转移性癌细胞释放细胞穿透荧光蛋白，这是由相邻的细胞，使空间识别的局部转移性细胞环境。使用该系统，可以在大块组织内鉴定和表征在转移性小生境中具有低代表性的组织细胞。为了突出其潜力，我们应用这种策略来研究肺中转移性乳腺癌细胞的细胞环境。我们报告了癌症相关实质细胞的存在，这些细胞表现出干细胞样特征、肺祖细胞标志物的表达、多谱系分化潜能和自我更新活性。在离体测定中，肺上皮细胞在与癌细胞共培养时获得癌症相关的实质细胞样表型并支持其生长。这些结果突出了这种方法作为新发现平台的潜力。
Direct investigation of the early cellular changes induced by metastatic cells within the surrounding tissue remains a challenge. Here we present a system in which metastatic cancer cells release a cell-penetrating fluorescent protein, which is taken up by neighbouring cells and enables spatial identification of the local metastatic cellular environment. Using this system, tissue cells with low representation in the metastatic niche can be identified and characterized within the bulk tissue. To highlight its potential, we applied this strategy to study the cellular environment of metastatic breast cancer cells in the lung. We report the presence of cancer-associated parenchymal cells, which exhibit stem-cell-like features, expression of lung progenitor markers, multi-lineage differentiation potential and self-renewal activity. In ex vivo assays, lung epithelial cells acquire a cancer-associated parenchymal-cell-like phenotype when co-cultured with cancer cells and support their growth. These results highlight the potential of this method as a platform for new discoveries.