A facile in vitro platform to study cancer cell dormancy under hypoxic microenvironments using CoCl(2).
A facile in vitro platform to study cancer cell dormancy under hypoxic microenvironments using CoCl(2).
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DOI：
10.1186/s13036-018-0106-7
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发表时间：
2018
影响因子：
5.6
通讯作者：
Azarin SM
中科院分区：
文献类型：
--
作者：
Lee HR;Leslie F;Azarin SM
虽然低氧在各种肿瘤微环境中已得到充分研究，但其在癌细胞休眠中的作用知之甚少，部分原因是缺乏完善的体外和体内模型。常规低氧室下的低氧条件相对不稳定，并且在室外表征期间不能维持，因为常氧反应很快建立。为了应对这一挑战，我们报告了一个强大的体外癌症休眠模型，在模拟缺氧的微环境下，使用氯化钴（CoCl 2），一种模拟缺氧的药物，稳定缺氧诱导因子1-α（HIF 1 α），缺氧信号的主要调节因子。我们比较了不同乳腺癌细胞系（MCF-7和MDA-MB-231）对CoCl 2和真实缺氧（0.1%O2）的细胞反应，以研究CoCl 2是否可以模拟乳腺癌休眠的缺氧调节。为此，在CoCl 2和真实缺氧下评估缺氧标志物HIF 1 α和GLUT 1以及增殖标志物Ki 67的表达水平、细胞生长、细胞周期分布以及蛋白质和基因表达。为了进一步验证我们的平台，还测试了卵巢癌细胞系OVCAR-3。我们的研究结果表明，氯化钴可以模拟MCF-7和MDA-MB-231乳腺癌细胞系中的癌症休眠的缺氧调节，重现这些细胞系在2D和3D中对真正缺氧的差异反应。此外，不同的基因表达谱在MCF-7和MDA-MB-231细胞CoCl 2处理下表明，关键的细胞周期成分的差异调节相同的缺氧应激。此外，CoCl 2处理下MCF-7细胞休眠的诱导是HIF 1 α依赖性的，如HIF 1 α抑制的MCF-7细胞在CoCl 2处理后不能表现出休眠行为所证明的。此外，CoCl 2还诱导并稳定维持OVCAR-3卵巢癌细胞的休眠。这些结果表明，这种基于氯化钴的模型可以提供一个广泛适用的体外平台，了解诱导缺氧应激下的癌细胞休眠。本文的在线版本（10.1186/s13036-018-0106-7）包含补充材料，可供授权用户使用。
While hypoxia has been well-studied in various tumor microenvironments, its role in cancer cell dormancy is poorly understood, in part due to a lack of well-established in vitro and in vivo models. Hypoxic conditions under conventional hypoxia chambers are relatively unstable and cannot be maintained during characterization outside the chamber since normoxic response is quickly established. To address this challenge, we report a robust in vitro cancer dormancy model under a hypoxia-mimicking microenvironment using cobalt chloride (CoCl2), a hypoxia-mimetic agent, which stabilizes hypoxia inducible factor 1-alpha (HIF1α), a major regulator of hypoxia signaling. We compared cellular responses to CoCl2 and true hypoxia (0.1% O2) in different breast cancer cell lines (MCF-7 and MDA-MB-231) to investigate whether hypoxic regulation of breast cancer dormancy could be mimicked by CoCl2. To this end, expression levels of hypoxia markers HIF1α and GLUT1 and proliferation marker Ki67, cell growth, cell cycle distribution, and protein and gene expression were evaluated under both CoCl2 and true hypoxia. To further validate our platform, the ovarian cancer cell line OVCAR-3 was also tested. Our results demonstrate that CoCl2 can mimic hypoxic regulation of cancer dormancy in MCF-7 and MDA-MB-231 breast cancer cell lines, recapitulating the differential responses of these cell lines to true hypoxia in 2D and 3D. Moreover, distinct gene expression profiles in MCF-7 and MDA-MB-231 cells under CoCl2 treatment suggest that key cell cycle components are differentially regulated by the same hypoxic stress. In addition, the induction of dormancy in MCF-7 cells under CoCl2 treatment is HIF1α-dependent, as evidenced by the inability of HIF1α-suppressed MCF-7 cells to exhibit dormant behavior upon CoCl2 treatment. Furthermore, CoCl2 also induces and stably maintains dormancy in OVCAR-3 ovarian cancer cells. These results demonstrate that this CoCl2-based model could provide a widely applicable in vitro platform for understanding induction of cancer cell dormancy under hypoxic stress. The online version of this article (10.1186/s13036-018-0106-7) contains supplementary material, which is available to authorized users.
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影响因子：
11.2
作者：
Harrison, Hannah;Rogerson, Lynsey;Landberg, Goran
通讯作者：
Landberg, Goran
影响因子：
4
作者：
de Prati, Alessandra Carcereri;Butturini, Elena;Mariotto, Sofia
通讯作者：
Mariotto, Sofia
影响因子：
56.9
作者：
GOLDBERG, MA;DUNNING, SP;BUNN, HF
通讯作者：
BUNN, HF
DOI：
10.1007/978-3-642-28160-0_2
发表时间：
2012-01-01
期刊：
Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer
影响因子：
--
作者：
Comen, Elizabeth;Norton, Larry
通讯作者：
Norton, Larry
影响因子：
21.3
作者：
通讯作者：
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