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Exploring cancer stem cell niche directed tumor growth.

机译：探索癌症干细胞生态位指导肿瘤生长。

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摘要

The finding that only a sub-fraction of tumor cells, so called Cancer Stem Cells (CSC), is endowed with the capacity to initiate new tumors has important consequences for fundamental as well as clinical cancer research. Previously we established by computational modeling techniques that CSC driven tumor growth instigates infiltrative behavior, and perhaps most interesting, stimulates tumor cell heterogeneity. An important question that remains is to what extend CSC functions are intrinsically regulated or whether this capacity is orchestrated by the microenvironment, i.e., a putative CSC niche. Here we investigate how extrinsic regulation of CSC properties affects the characteristics of malignancies. We find that highly invasive growth in tumors dependent on a small subset of cells is not restricted to CSC-driven tumors, but is also observed in tumors where the CSC capacity of tumor cells is completely defined by the microenvironment. Importantly, also the high level of heterogeneity that was observed for CSC-driven tumors is preserved and partially even increased in malignancies with a microenvironmentally orchestrated CSC population. This indicates that invasive growth and high heterogeneity are fundamental properties of tumors fueled by a small population of tumor cells.
机译：仅肿瘤细胞的一小部分，即所谓的癌症干细胞（CSC），才具有启动新肿瘤的能力，这一发现对基础以及临床癌症研究都具有重要意义。以前，我们通过计算建模技术确定，CSC驱动的肿瘤生长可激发浸润行为，并且也许最有趣的是刺激肿瘤细胞异质性。剩下的一个重要问题是，CSC功能在哪些方面得到内在调节，或者这种能力是否由微环境（即推定的CSC生态位）来协调。在这里，我们研究了CSC属性的外部调节如何影响恶性肿瘤的特征。我们发现依赖于一小部分细胞的肿瘤中的高侵袭性生长不仅限于CSC驱动的肿瘤，而且在肿瘤细胞的CSC能力完全由微环境定义的肿瘤中也观察到。重要的是，在由微环境精心策划的CSC人群的恶性肿瘤中，CSC驱动的肿瘤所观察到的高度异质性也得以保留，甚至部分增加。这表明侵袭性生长和高异质性是由少量肿瘤细胞推动的肿瘤的基本特性。

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