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High-resolution spatiotemporal pHe and pO2 imaging in head and neck and oesophageal carcinoma cells
Cancer & Metabolism ( IF 6.0 ) Pub Date : 2021-05-04 , DOI: 10.1186/s40170-021-00257-6
Alexandra Blancke Soares , Robert Meier , Gregor Liebsch , Sabina Schwenk-Zieger , Martin E. Kirmaier , Sebastian Theurich , Magdalena Widmann , Martin Canis , Olivier Gires , Frank Haubner

pO2 and pH are physiological parameters relevant for different processes in health and disease, including wound healing and cancer progression. Head and neck squamous cell carcinomas (HNSCC) and oesophageal squamous cell carcinomas (ESCC) have a high rate of local recurrence that is partly related to treatment-resistant residual tumour cells. Hence, novel diagnostic tools are required to visualise potential residual tumour cells and thereby improve treatment outcome for HNSCC and ESCC patients. We developed a device to spatiotemporally measure oxygen consumption rates (OCR) and extracellular acidification rates (ECAR) to distinguish HNSCC and ESCC cells from healthy cells in vitro, exploiting general metabolic differences between cancer cells and healthy cells. OCR and ECAR were measured via a newly developed device named STO2p-Q (SpatioTemporal O2 and pH Quantification) using the VisiSens technology based on ratiometric fluorescence imaging, facilitating spatiotemporal resolution. Results were confirmed using extracellular flux analyses (Seahorse technology). STO2p-Q is described and used to measure OCR and ECAR in HNSCC and ESCC cell lines and normal fibroblast and epithelial cells as components of the tumour microenvironment. OCR measurements showed differences amongst HNSCC and ESCC cell lines and between HNSCC/ESCC and normal cells, which on average had lower OCR than HNSCC/ESCC cells. Both OCR and ECAR measurements were independently verified using the Seahorse technology. Additionally, using STO2p-Q, HNSCC/ESCC, and normal cells could be spatially resolved with a resolution in the low millimetre range. We developed a method to spatiotemporally measure OCR and ECAR of cells, which has many potential in vitro applications and lays the foundation for the development of novel diagnostic tools for the detection of cancerous tissue in HNSCC and ESCC patients in vivo.

中文翻译:

头颈和食管癌细胞的高分辨率时空pH e和pO 2成像

pO2和pH是与健康和疾病的不同过程相关的生理参数,包括伤口愈合和癌症进展。头颈部鳞状细胞癌(HNSCC)和食道鳞状细胞癌(ESCC)具有较高的局部复发率,这部分与耐药性残留肿瘤细胞有关。因此,需要新颖的诊断工具来可视化潜在的残留肿瘤细胞,从而改善HNSCC和ESCC患者的治疗效果。我们开发了一种设备,可利用时空测量氧气消耗率(OCR)和细胞外酸化率(ECAR)来区分HNSCC和ESCC细胞与体外健康细胞,从而利用癌细胞与健康细胞之间的一般代谢差异。使用基于比率荧光成像的VisiSens技术,通过名为STO2p-Q(时空O2和pH定量)的新开发设备测量OCR和ECAR,以促进时空分辨率。使用细胞外通量分析(Seahorse技术)确认了结果。STO2p-Q已被描述并用于测量HNSCC和ESCC细胞系以及正常成纤维细胞和上皮细胞中的OCR和ECAR,它们是肿瘤微环境的组成部分。OCR测量显示HNSCC和ESCC细胞系之间以及HNSCC / ESCC和正常细胞之间的差异,其平均OCR低于HNSCC / ESCC细胞。OCR和ECAR测量均使用Seahorse技术独立进行了验证。此外,使用STO2p-Q,HNSCC / ESCC,正常细胞可以在低毫米范围内进行空间分辨。我们开发了一种时空测量细胞OCR和ECAR的方法,该方法在体外具有许多潜在应用,并为开发新的诊断工具用于体内检测HNSCC和ESCC患者的癌组织奠定了基础。
更新日期:2021-05-05
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