MDA-MB-231 Breast Cancer Cells and Their CSC Population Migrate Towards Low Oxygen in a Microfluidic Gradient Device.
MDA-MB-231 Breast Cancer Cells and Their CSC Population Migrate Towards Low Oxygen in a Microfluidic Gradient Device.
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DOI：
10.3390/ijms19103047
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发表时间：
2018-10-06
影响因子：
5.6
通讯作者：
Sahlgren CM
中科院分区：
文献类型：
--
作者：
Sleeboom JJF;Toonder JMJD;Sahlgren CM
大多数癌症死亡是由转移形成的继发性肿瘤引起的，但由于我们对这一过程的了解有限，预防仍然是一个重大挑战。最近，肿瘤干细胞(CSCs)被认为是肿瘤转移的来源，但人们对其迁移行为知之甚少。肿瘤中的氧梯度与乳腺癌细胞的定向迁移有关。在这里，我们提出了一种方法来研究氧气梯度对乳腺CSCs迁移行为的影响。我们的芯片包含一个小室，可以在低氧(1%)和环境(21%)条件下产生氧气梯度。我们跟踪了从MDA-MB-231乳腺癌细胞中获得的CSCs的迁移情况，发现它们的迁移模式与平均的MDA-MB-231群体没有什么不同。令人惊讶的是，我们发现细胞迁移到低氧水平，与早期的研究形成对比。我们假设，在我们的设备中，迁移完全是由于纯氧梯度，而早期工作中氧的影响被来自肿瘤微环境的额外线索(例如，营养物质和代谢物)所掩盖。这些结果为氧在指导癌症和CSC迁移中的作用开辟了新的研究方向。
Most cancer deaths are caused by secondary tumors formed through metastasis, yet due to our limited understanding of this process, prevention remains a major challenge. Recently, cancer stem cells (CSCs) have been proposed as the source of metastases, but only little is known about their migratory behavior. Oxygen gradients in the tumor have been linked to directional migration of breast cancer cells. Here, we present a method to study the effect of oxygen gradients on the migratory behavior of breast CSCs using a microfluidic device. Our chip contains a chamber in which an oxygen gradient can be generated between hypoxic (<1%) and ambient (21%) conditions. We tracked the migration of CSCs obtained from MDA-MB-231 breast cancer cells, and found that their migration patterns do not differ from the average MDA-MB-231 population. Surprisingly, we found that the cells migrate towards low oxygen levels, in contrast with an earlier study. We hypothesize that in our device, migration is exclusively due to the pure oxygen gradient, whereas the effects of oxygen in earlier work were obscured by additional cues from the tumor microenvironment (e.g., nutrients and metabolites). These results open new research directions into the role of oxygen in directing cancer and CSC migration.
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