J Cancer 2021; 12(19):5817-5824. doi:10.7150/jca.56307 This issue Cite

Research Paper

OxLDL as an Inducer of a Metabolic Shift in Cancer Cells

Albert V. Bitorina1*, Yvonne Oligschlaeger1*, Lingling Ding1, Tulasi Yadati1, Annemarie Westheim3, Tom Houben1, Rianne D.W. Vaes2, Steven W.M. Olde Damink2, Jan Theys3✉, Ronit Shiri-Sverdlov1✉

1. Department of Molecular Genetics, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands.
2. Department of Surgery, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands.
3. Department of Precision Medicine, School for Oncology & Developmental Biology (GROW), Maastricht University Medical Centre, Maastricht, Netherlands.
*These authors contributed equally to this work; #Shared last authors.

Citation:
Bitorina AV, Oligschlaeger Y, Ding L, Yadati T, Westheim A, Houben T, Vaes RDW, Olde Damink SWM, Theys J, Shiri-Sverdlov R. OxLDL as an Inducer of a Metabolic Shift in Cancer Cells. J Cancer 2021; 12(19):5817-5824. doi:10.7150/jca.56307. https://www.jcancer.org/v12p5817.htm
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Abstract

Graphic abstract

Recent evidence established a link between disturbed lipid metabolism and increased risk for cancer. One of the most prominent features related to disturbed lipid metabolism is an increased production of oxidized low-density-lipoproteins (oxLDL), which results from elevated oxidative stress. OxLDL is known to have detrimental effects on healthy cells and plays a primary role in diseases related to the metabolic syndrome. Nevertheless, so far, the exact role of oxLDL in cancer cell metabolism is not yet known. To examine changes in metabolic profile induced by oxLDL, pancreatic KLM-1 cells were treated with oxLDL in a concentration- (25 or 50 µg/ml) and/or time-dependent (4 hr or 8 hr) manner and the impact of oxLDL on oxygen consumption rates (OCR) as well as extracellular acidification rates (ECAR) was analyzed using Seahorse technology. Subsequently, to establish the link between oxLDL and glycolysis, stabilization of the master regulator hypoxia-inducible factor 1-alpha (HIF-1α) was measured by means of Western blot. Furthermore, autophagic responses were assessed by measuring protein levels of the autophagosomal marker LC3B-II. Finally, the therapeutic potential of natural anti-oxLDL IgM antibodies in reversing these effects was tested. Incubation of KLM-1 cells with oxLDL shifted the energy balance towards a more glycolytic phenotype, which is an important hallmark of cancer cells. These data were supported by measurement of increased oxLDL-mediated HIF-1α stabilization. In line, oxLDL incubation also increased the levels of LC3B-II, suggesting an elevated autophagic response. Importantly, antibodies against oxLDL were able to reverse these oxLDL-mediated metabolic effects. Our data provides a novel proof-of-concept that oxLDL induces a shift in energy balance. These data not only support a role for oxLDL in the progression of cancer but also suggest the possibility of targeting oxLDL as a therapeutic option in cancer.

Keywords: Pancreatic cancer cells, oxLDL, metabolic switch, HIF-1α, autophagy


Citation styles

APA
Bitorina, A.V., Oligschlaeger, Y., Ding, L., Yadati, T., Westheim, A., Houben, T., Vaes, R.D.W., Olde Damink, S.W.M., Theys, J., Shiri-Sverdlov, R. (2021). OxLDL as an Inducer of a Metabolic Shift in Cancer Cells. Journal of Cancer, 12(19), 5817-5824. https://doi.org/10.7150/jca.56307.

ACS
Bitorina, A.V.; Oligschlaeger, Y.; Ding, L.; Yadati, T.; Westheim, A.; Houben, T.; Vaes, R.D.W.; Olde Damink, S.W.M.; Theys, J.; Shiri-Sverdlov, R. OxLDL as an Inducer of a Metabolic Shift in Cancer Cells. J. Cancer 2021, 12 (19), 5817-5824. DOI: 10.7150/jca.56307.

NLM
Bitorina AV, Oligschlaeger Y, Ding L, Yadati T, Westheim A, Houben T, Vaes RDW, Olde Damink SWM, Theys J, Shiri-Sverdlov R. OxLDL as an Inducer of a Metabolic Shift in Cancer Cells. J Cancer 2021; 12(19):5817-5824. doi:10.7150/jca.56307. https://www.jcancer.org/v12p5817.htm

CSE
Bitorina AV, Oligschlaeger Y, Ding L, Yadati T, Westheim A, Houben T, Vaes RDW, Olde Damink SWM, Theys J, Shiri-Sverdlov R. 2021. OxLDL as an Inducer of a Metabolic Shift in Cancer Cells. J Cancer. 12(19):5817-5824.

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