Amsterdam UMC, University of Amsterdam, LEXOR, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam and Amsterdam Gastroenterology & Metabolism, Amsterdam, The Netherlands.
Cancer Research UK, Cambridge Institute, University of Cambridge, Cambridge, UK.
Nat Cell Biol. 2018 Oct;20(10):1193-1202. doi: 10.1038/s41556-018-0179-z. Epub 2018 Sep 3.
Solid malignancies have been speculated to depend on cancer stem cells (CSCs) for expansion and relapse after therapy. Here we report on quantitative analyses of lineage tracing data from primary colon cancer xenograft tissue to assess CSC functionality in a human solid malignancy. The temporally obtained clone size distribution data support a model in which stem cell function in established cancers is not intrinsically, but is entirely spatiotemporally orchestrated. Functional stem cells that drive tumour expansion predominantly reside at the tumour edge, close to cancer-associated fibroblasts. Hence, stem cell properties change in time depending on the cell location. Furthermore, although chemotherapy enriches for cells with a CSC phenotype, in this context functional stem cell properties are also fully defined by the microenvironment. To conclude, we identified osteopontin as a key cancer-associated fibroblast-produced factor that drives in situ clonogenicity in colon cancer.
实体恶性肿瘤被推测依赖于癌症干细胞 (CSCs) 在治疗后进行扩增和复发。在这里，我们报告了对原发性结肠癌异种移植组织中谱系追踪数据的定量分析，以评估人类实体恶性肿瘤中 CSC 的功能。随时间获得的克隆大小分布数据支持这样一种模型，即在已建立的癌症中，干细胞功能不是内在的，而是完全受时空调节的。驱动肿瘤扩张的功能干细胞主要位于肿瘤边缘，靠近癌相关成纤维细胞。因此，干细胞特性随时间而变化，取决于细胞位置。此外，尽管化疗富集了具有 CSC 表型的细胞，但在这种情况下，功能干细胞特性也完全由微环境定义。总之，我们确定了骨桥蛋白是一种关键的癌相关成纤维细胞产生的因子，它可以在结肠癌中驱动原位克隆形成。
