School of Medicine, Ophthalmology, Visual and Anatomical Sciences, Wayne State University, Detroit, MI, USA.
Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
Methods Mol Biol. 2023;2575:275-295. doi: 10.1007/978-1-0716-2716-7_14.
Tumors are usually associated with oxygen-deficient regions (hypoxia) which results from reduced and disorganized intratumoral vasculature, increased diffusion distances, and growing tumor masses. The proteomic and metabolomic landscape of the hypoxic cells is reprogrammed through hypoxia-induced transcription factor 1 which is activated in hypoxic conditions and is inactive when oxygen is abundant. This transcription factor has also been shown to inhibit or even reverse cell differentiation. Hypoxia impedes chemotherapy as it hampers the formation of cytotoxic free radicals due to the lesser availability of molecular oxygen. The metastatic and invasive attributes of cancer cells in hypoxic conditions are exacerbated, which results in poor therapeutic outcomes. Various cell-based assays for measuring hypoxia have been developed which give an estimate of the hypoxic state of cancer cells. Prior knowledge of these assays will improve the efficacy of the treatment regimens for cancers. This article provides exhaustive information on the hypoxia-based assays which are sensitive, robust, reliable, and give easy readout with choice of cell type for these assays may be dictated by the procedural or endpoint selection.
肿瘤通常与缺氧区域(缺氧)相关,这是由于肿瘤内血管减少和紊乱、扩散距离增加以及肿瘤生长导致的。缺氧诱导转录因子 1 可重新编程缺氧细胞的蛋白质组学和代谢组学景观,该转录因子在缺氧条件下被激活,而在氧气充足时则不活跃。该转录因子还被证明可以抑制甚至逆转细胞分化。缺氧会阻碍化疗,因为由于分子氧的可用性较低,会阻碍细胞毒性自由基的形成。在缺氧条件下,癌细胞的转移和侵袭特性会加剧,从而导致治疗效果不佳。已经开发出各种基于细胞的测定方法来测量缺氧,这些方法可以估计癌细胞的缺氧状态。了解这些测定方法可以提高癌症治疗方案的疗效。本文提供了基于缺氧的测定方法的详尽信息,这些方法具有敏感性、稳健性、可靠性,并且易于读取,选择这些测定方法的细胞类型可能取决于程序或终点选择。