人舌癌前发育不良口腔角质形成细胞和鳞状癌细胞生物能量学的比较
A comparison of bioenergetics in human tongue pre-cancerous dysplastic oral keratinocytes and squamous cancer cells.
Keywords:oral squamous cancer cells;mitochondria;interleukin 6;dysplastic oral keratinocytes;oxygen consumption
关键词:口腔鳞状癌细胞;线粒体;白细胞介素 6;发育不良的口腔角质形成细胞;耗氧量
哺乳动物:人
细胞:内皮细胞;上皮细胞;间皮细胞
作者:Karavyraki Marilena、Gnaiger Erich、Porter Richard K
出版期刊:《MitoFit Preprints 》( 2022)
Abstract:
In an endeavour to understand the metabolic phenotype behind oral squamous cell carcinomas, we characterised the bioenergetic profile of a human tongue derived cancer cell line (SCC-4 cells) and compared this profile to a pre-cancerous dysplastic oral keratinocyte (DOK) cell line also derived from human tongue. The human SCC-4 cancer cells had greater mitochondrial densitydensity but lower mitochondrial O2 flow per cell than DOK cells. The lower oxygen consumption rate in SCC-4 cells can be partially explained by lower NADH-related enzymatic activity and lower mitochondrial Complex I activity when compared to pre-cancerous DOK cells. In addition, SCC-4 cells have greater extracellular acidification rate (an index of glycolytic flux) when compared to DOK cells. In addition, treatment with recombinant human IL-6 (rhIL-6), known to drive anoikis resistance in SCC-4 cells but not DOK cells, impairs oxygen consumption in SCC-4 but not DOK cells, without affecting mitochondrial density. We conclude that SCC-4 cells have a less oxidative phenotype compared to DOK cells and that IL-6 attenuates mitochondrial function in SCC-4 cells while increasing glycolytic flux.
文章摘要:
为了了解口腔鳞状细胞癌背后的代谢表型,我们对人类舌源性癌细胞系(SCC-4 细胞)的生物能量特征进行了表征,并将该特征与癌前发育不良口腔角质形成细胞 (DOK) 细胞进行了比较线也来源于人的舌头。与 DOK 细胞相比,人类 SCC-4 癌细胞的线粒体密度密度更高,但每个细胞的线粒体 O2 流量更低。与癌前 DOK 细胞相比,SCC-4 细胞中较低的耗氧率可以部分解释为较低的 NADH 相关酶活性和较低的线粒体复合物 I 活性。此外,与 DOK 细胞相比,SCC-4 细胞具有更高的细胞外酸化率(糖酵解通量的指标)。此外,用重组人 IL-6 (rhIL-6) 治疗,已知驱动 SCC-4 细胞而不是 DOK 细胞中的失巢凋亡抗性,损害 SCC-4 而不是 DOK 细胞中的氧消耗,而不影响线粒体密度。我们得出结论,与 DOK 细胞相比,SCC-4 细胞具有较少的氧化表型,并且 IL-6 减弱了 SCC-4 细胞中的线粒体功能,同时增加了糖酵解通量。
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