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Abstract
Besides playing a crucial role in immune surveillance, human leukocyte antigens (HLA) possess numerous non-immune functions involved in cell communication. In the present study, screening of a panel of HLA class I- and HLA class II-specific monoclonal antibodies (mAbs) for their effects on the metabolism of human melanoma cells showed for the first time that the HLA-B,C-specific mAb B1.23.2 reduced the expression level of key glycolytic enzymes, but did not affect that of mitochondrial respiration effectors. As a result, the metabolism of melanoma cells shifted from a Warburg metabolism to a more oxidative phosphorylation. In addition, the HLA-B,C-specific mAb B1.23.2 downregulated the expression of glutamine transporter and glutaminase enzyme participating in the reduction of tricarboxylic acid cycle. The HLA-B,C-specific mAb B1.23.2-mediated reduction in energy production was associated with a reduction of melanoma cell motility. On the whole, the described results suggest that HLA class I antigens, and in particular the gene products of HLA-B and C loci play a role in the motility of melanoma cells by regulating their metabolism.
Highlights
The activation of signaling pathways that alter metabolism of tumor cells plays a major role in tumor progression
In this study we have screened human leukocyte antigens (HLA)-specific monoclonal antibodies (mAbs) for their effects on the metabolic activity of cultured human melanoma cells and we have found for the first time that the HLA-B,C-specific mAb B1.23.2 inhibits glycolysis
To prove that the effects we have described were caused by interactions of the HLA-B,C-specific mAb B1.23.2 with the gene products of the HLA-B and C loci and not with unrelated molecules, we tested whether the HLA-B,C-specific mAb B1.23.2 had any effects on the metabolism of FO-1 melanoma cells
Summary
The activation of signaling pathways that alter metabolism of tumor cells plays a major role in tumor progression. In contrast to normal cells, which rely on mitochondrial oxidative phosphorylation to generate energy needed for cellular processes, most cancer cells keep glycolysis highly activated even under aerobic conditions, a phenomenon termed “Warburg effect” [1,2]. This constitutive feature associated with exogenous supply of glutamine, which serves to replenish tricarboxylic acid cycle, may sustain relentless proliferation of cancer cells. This metabolic reprogramming is most often combined with an ineffective blood supply. The metabolic dynamic adaptation of tumor cells in different microenvironments represents one of the hallmarks of malignancy
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