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10.3390/ijms22041805
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Article

Differences in the Central Energy Metabolism of Cancer Cells between Conventional 2D and Novel 3D Culture Systems

by
Ryo Ikari
1,
Ken-ichi Mukaisho
2,*,
Susumu Kageyama
1,
Masayuki Nagasawa
1,
Shigehisa Kubota
1,
Takahisa Nakayama
2,
Shoko Murakami
3,
Naoko Taniura
2,
Hiroyuki Tanaka
4,
Ryoji P. Kushima
2 and
Akihiro Kawauchi
1
1
Department of Urology, Shiga University of Medical Science, Otsu 520-2192, Japan
2
Division of Human Pathology, Department of Pathology, Shiga University of Medical Science, Otsu 520-2192, Japan
3
Department of Oral and Maxillofacial Surgery, Shiga University of Medical Science, Otsu 520-2192, Japan
4
Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Otsu 520-2192, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(4), 1805; https://doi.org/10.3390/ijms22041805
Submission received: 31 December 2020 / Revised: 7 February 2021 / Accepted: 8 February 2021 / Published: 11 February 2021
(This article belongs to the Special Issue Development of Cell Culture Technology: Molecular Aspects and Beyond)
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Abstract

The conventional two-dimensional (2D) culture is available as an in vitro experimental model. However, the culture system reportedly does not recapitulate the in vivo cancer microenvironment. We recently developed a tissueoid cell culture system using Cellbed, which resembles the loose connective tissue in living organisms. The present study performed 2D and three-dimensional (3D) culture using prostate and bladder cancer cell lines and a comprehensive metabolome analysis. Compared to 3D, the 2D culture had significantly lower levels of most metabolites. The 3D culture system did not impair mitochondrial function in the cancer cells and produce energy through the mitochondria simultaneously with aerobic glycolysis. Conversely, ATP production, biomass (nucleotides, amino acids, lipids and NADPH) synthesis and redox balance maintenance were conducted in 3D culture. In contrast, in 2D culture, biomass production was delayed due to the suppression of metabolic activity. The 3D metabolome analysis using the tissueoid cell culture system capable of in vivo cancer cell culture yielded results consistent with previously reported cancer metabolism theories. This system is expected to be an essential experimental tool in a wide range of cancer research fields, especially in preclinical stages while transitioning from in vitro to in vivo.
Keywords: cancer metabolism; three-dimensional; tissueoid cell culture system; urinary bladder cancer; prostate cancer cancer metabolism; three-dimensional; tissueoid cell culture system; urinary bladder cancer; prostate cancer

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MDPI and ACS Style

Ikari, R.; Mukaisho, K.-i.; Kageyama, S.; Nagasawa, M.; Kubota, S.; Nakayama, T.; Murakami, S.; Taniura, N.; Tanaka, H.; Kushima, R.P.; et al. Differences in the Central Energy Metabolism of Cancer Cells between Conventional 2D and Novel 3D Culture Systems. Int. J. Mol. Sci. 2021, 22, 1805. https://doi.org/10.3390/ijms22041805

AMA Style

Ikari R, Mukaisho K-i, Kageyama S, Nagasawa M, Kubota S, Nakayama T, Murakami S, Taniura N, Tanaka H, Kushima RP, et al. Differences in the Central Energy Metabolism of Cancer Cells between Conventional 2D and Novel 3D Culture Systems. International Journal of Molecular Sciences. 2021; 22(4):1805. https://doi.org/10.3390/ijms22041805

Chicago/Turabian Style

Ikari, Ryo, Ken-ichi Mukaisho, Susumu Kageyama, Masayuki Nagasawa, Shigehisa Kubota, Takahisa Nakayama, Shoko Murakami, Naoko Taniura, Hiroyuki Tanaka, Ryoji P. Kushima, and et al. 2021. "Differences in the Central Energy Metabolism of Cancer Cells between Conventional 2D and Novel 3D Culture Systems" International Journal of Molecular Sciences 22, no. 4: 1805. https://doi.org/10.3390/ijms22041805

APA Style

Ikari, R., Mukaisho, K.-i., Kageyama, S., Nagasawa, M., Kubota, S., Nakayama, T., Murakami, S., Taniura, N., Tanaka, H., Kushima, R. P., & Kawauchi, A. (2021). Differences in the Central Energy Metabolism of Cancer Cells between Conventional 2D and Novel 3D Culture Systems. International Journal of Molecular Sciences, 22(4), 1805. https://doi.org/10.3390/ijms22041805

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