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Issue 19, 2020
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Oxygen consumption rate of tumour spheroids during necrotic-like core formation

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Abstract

Hypoxia is one of the major hallmarks of solid tumours and is associated with the poor prognosis of various cancers. A multicellular aggregate, termed a spheroid, has been used as a tumour model with a necrotic-like core for more than 45 years. Oxygen metabolism in spheroids has been studied using phosphorescence quenching and oxygen-sensitive electrodes. However, these conventional methods require chemical labelling and physical insertion of the electrode into each spheroid, which may be functionally and structurally disruptive. Scanning electrochemical microscopy (SECM) can non-invasively analyse oxygen metabolism. Here, we used SECM to investigate whether the changes of the internal structure of spheroids affect the oxygen metabolism. We investigated the oxygen consumption rate (OCR) of MCF-7 breast tumour spheroids with and without a necrotic-like core. A numerical simulation was used to describe a method for estimating the OCR of spheroids that settled at the bottom of the conventional culture plates. The OCR per spheroid volume decreased with increasing spheroid radius, indicating the limitation of the oxygen supply to the core of the MCF-7 spheroid. Formation of the necrotic-like core did not affect the oxygen metabolism significantly, implying that the core had minimal contribution to the OCR even before necrosis occurred. OCR analysis using SECM non-invasively monitors the change of oxygen metabolism in tumour spheroids. The approach is promising to evaluate various three-dimensional culture models.

Graphical abstract: Oxygen consumption rate of tumour spheroids during necrotic-like core formation

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Supplementary files

Article information


Submitted
14 May 2020
Accepted
15 Jul 2020
First published
20 Jul 2020

Analyst, 2020,145, 6342-6348
Article type
Paper

Oxygen consumption rate of tumour spheroids during necrotic-like core formation

R. Mukomoto, Y. Nashimoto, T. Terai, T. Imaizumi, K. Hiramoto, K. Ino, R. Yokokawa, T. Miura and H. Shiku, Analyst, 2020, 145, 6342
DOI: 10.1039/D0AN00979B

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