Fatty Acid β-Oxidation-dependent and -independent Responses and Tumor Aggressiveness Acquired Under Mild Hypoxia

Abstract

Background/aim: The present study assessed whether and how tumor cells undergoing hypoxia contribute to disease progression after moving to areas with different oxygen conditions.

Materials and methods: Human colorectal carcinoma HCT116 cells cultured under mild hypoxia were subjected to in vivo experiments using transfer to immunodeficient murine recipients and to in vitro experiments using pharmacological inhibition of fatty acid β-oxidation (FAO).

Results: Bone involvement and hepatic metastases were accelerated in transfer models of hypoxically cultured HCT116 cells. Hypoxic HCT116 cells exhibited FAO-dependent glycogen synthesis. FAO-dependent and -independent induction of gene expression also occurred under hypoxia. The distribution of glucose transporter 1 expression compared with heme oxygenase 1 expression in HCT116 cell spheroids seemed consistent with differential dependence of hypoxic expression of these molecules on FAO.

Conclusion: These results provide insights into the contribution of hypoxia to tumor progression and the relevance of FAO.

Keywords: Hypoxia; cell spheroids; fatty acid β-oxidation; glycogen synthesis; human colorectal carcinoma HCT116 cells; transcriptomic profiles; tumor aggressiveness.