Oxygen Partial Pressure Is a Rate-Limiting Parameter for Cell Proliferation in 3D Spheroids Grown in Physioxic Culture Condition.
Oxygen Partial Pressure Is a Rate-Limiting Parameter for Cell Proliferation in 3D Spheroids Grown in Physioxic Culture Condition.
复制标题
DOI：
10.1371/journal.pone.0161239
复制
发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Ducommun B
中科院分区：
文献类型：
--
作者：
Gomes A;Guillaume L;Grimes DR;Fehrenbach J;Lobjois V;Ducommun B
正常和肿瘤组织中的原位氧分压在百分之几的范围内。因此，当研究3D培养系统中的细胞生长时，必须考虑生理氧浓度而不是环境空气中的氧浓度如何影响增殖参数。在这里，我们研究了将氧分压从21%降低到5%对3D肿瘤球体模型中的细胞增殖率和区域化的影响。我们发现，与21%氧气浓度下的培养相比，5%氧气浓度强烈抑制球状体生长，改变增殖梯度并降低50%深度增殖指数（IDP 50）。然后，我们模拟的氧分压分布使用的实验数据，通过培养球状体在物理氧和常氧条件下。虽然缺氧发生在类似的深度在两种条件下生长的球体，氧分压是一个主要的限速因素，细胞增殖率和区域化的关键影响，只有在physioxic条件下生长的球体，而不是在大气中常氧生长的球体。我们的发现加强了考虑在物理氧化条件下进行实验的必要性（即，组织常氧），用于正确理解癌细胞生物学和评价3D培养系统中的抗癌药物。
The in situ oxygen partial pressure in normal and tumor tissues is in the range of a few percent. Therefore, when studying cell growth in 3D culture systems, it is essential to consider how the physiological oxygen concentration, rather than the one in the ambient air, influences the proliferation parameters. Here, we investigated the effect of reducing oxygen partial pressure from 21% to 5% on cell proliferation rate and regionalization in a 3D tumor spheroid model. We found that 5% oxygen concentration strongly inhibited spheroid growth, changed the proliferation gradient and reduced the 50% In Depth Proliferation index (IDP50), compared with culture at 21% oxygen. We then modeled the oxygen partial pressure profiles using the experimental data generated by culturing spheroids in physioxic and normoxic conditions. Although hypoxia occurred at similar depth in spheroids grown in the two conditions, oxygen partial pressure was a major rate-limiting factor with a critical effect on cell proliferation rate and regionalization only in spheroids grown in physioxic condition and not in spheroids grown at atmospheric normoxia. Our findings strengthen the need to consider conducting experiment in physioxic conditions (i.e., tissue normoxia) for proper understanding of cancer cell biology and the evaluation of anticancer drugs in 3D culture systems.
登录
查看更多内容
影响因子：
3.8
作者：
Laurent J;Frongia C;Cazales M;Mondesert O;Ducommun B;Lobjois V
通讯作者：
Lobjois V
影响因子：
3.5
作者：
Grimes DR;Fletcher AG;Partridge M
通讯作者：
Partridge M
影响因子：
8.8
作者：
KOCH, CJ;EVANS, SM;LORD, EM
通讯作者：
LORD, EM
影响因子：
5.3
作者：
Carreau A;El Hafny-Rahbi B;Matejuk A;Grillon C;Kieda C
通讯作者：
Kieda C
DOI：
10.1098/rsif.2013.1124
发表时间：
2014-03-06
期刊：
Journal of the Royal Society, Interface
影响因子：
--
作者：
Grimes DR;Kelly C;Bloch K;Partridge M
通讯作者：
Partridge M