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Cancers (Basel). 2019 Aug 26;11(9). doi: 10.3390/cancers11091249.

Potential Role of HLA Class I Antigens in the Glycolytic Metabolism and Motility of Melanoma Cells.

Cancers

Silvia Peppicelli, Jessica Ruzzolini, Elena Andreucci, Francesca Bianchini, Filippos Kontos, Teppei Yamada, Soldano Ferrone, Lido Calorini

Affiliations

  1. Department of Experimental and Clinical Biomedical Sciences "Mario Serio", Section of Experimental Pathology and Oncology, Viale G.B. Morgagni, 50-50134, Florence, Italy. [email protected].
  2. Department of Experimental and Clinical Biomedical Sciences "Mario Serio", Section of Experimental Pathology and Oncology, Viale G.B. Morgagni, 50-50134, Florence, Italy.
  3. Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  4. Department of Experimental and Clinical Biomedical Sciences "Mario Serio", Section of Experimental Pathology and Oncology, Viale G.B. Morgagni, 50-50134, Florence, Italy. [email protected].
  5. Istituto Toscano Tumori and Center of Excellence for Research, Transfer and High Education DenoTHE University of Florence, Piazza di San Marco, 4, 50121 Florence, Italy. [email protected].

PMID: 31454998 PMCID: PMC6770395 DOI: 10.3390/cancers11091249

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.

Keywords: HLA class I; glycolytic metabolism; melanoma cells; motility

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the dec

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