Similarities and differences in metabolites of tongue cancer cells among two- and three-dimensional cultures and xenografts.

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Because the 3D culture shows a structure similar to that of in

vivo conditions, the interactions between cancer cells were in effect

and several metabolites were present at levels that were comparable to those in the xenografts. However, as the in vivo environment

maintains blood flow in the cancer tissue, the host metabolites can

exert an influence. Thus, the levels of decomposition products of

purine nucleotides, such as xanthine and uric acid, decomposition

products of the liver, such as urea, and metabolic intermediates of

choline to glycine, which are abundant in muscle and body tissues,

were high only in the xenografts. From these results, we will try to

establish coculture of cancer and stroma cells even in 3D culture in

the near future, but we also need to consider the effect of blood

flow. However, this 3D tissueoid cell culture system is much better

than 2D culture and is expected to be used in a wide range of fields

within cancer research.

Based on the present results, unlike in the 3D culture, there

were almost no glycolytic intermediates in the xenografts.

Although lactic acid, produced by glycolysis, is excreted from

cancer cells in the in vivo environment, the lactic acid could be

used for angiogenesis and other processes by interaction with the

tumor stroma. 29 Additionally, we inferred that cancer cells were

reusing lactic acid and converting it to pyruvate before using it in

the TCA cycle.

In summary, the cancer cells in the 3D culture and xenografts

were shown to actively conduct glycolysis and the citric acid cycle,

using nutrients like glucose, for biomass biosynthesis and ATP production by oxidative phosphorylation, as well as to maintain the

redox balance. Conversely, the results from the 2D system suggest

that a unique form of metabolism was used to enable cell survival

under conditions different from the in vivo environment. The 3D

metabolome analysis capable of mimicking the morphology and

function of in vivo cancer cells yielded results consistent with previously reported theories of cancer metabolism.

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S U P P O R T I N G I N FO R M AT I O N

Additional supporting information may be found online in the

Supporting Information section.

How to cite this article: Murakami S, Tanaka H, Nakayama T,

et al. Similarities and differences in metabolites of tongue

cancer cells among two- and three-dimensional cultures and

xenografts. Cancer Sci. 2020;00:1–14. https://doi.

org/10.1111/cas.14749

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