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BMC Cancer
Published in: BMC Cancer 1/2024

Open Access 01-12-2024 | Acute Myeloid Leukemia | Research

TIM-3/Galectin-9 interaction and glutamine metabolism in AML cell lines, HL-60 and THP-1

Authors: Hooriyeh Shapourian, Mustafa Ghanadian, Nahid Eskandari, Abolfazl Shokouhi, Gülderen Yanikkaya Demirel, Alexandr V. Bazhin, Mazdak Ganjalikhani-Hakemi

Published in: BMC Cancer | Issue 1/2024

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Abstract

Background

T cell immunoglobulin and mucin-domain containing-3 (TIM-3) is a cell surface molecule that was first discovered on T cells. However, recent studies revealed that it is also highly expressed in acute myeloid leukemia (AML) cells and it is related to AML progression. As, Glutamine appears to play a prominent role in malignant tumor progression, especially in their myeloid group, therefore, in this study we aimed to evaluate the relation between TIM-3/Galectin-9 axis and glutamine metabolism in two types of AML cell lines, HL-60 and THP-1.

Methods

Cell lines were cultured in RPMI 1640 which supplemented with 10% FBS and 1% antibiotics. 24, 48, and 72 h after addition of recombinant Galectin-9 (Gal-9), RT-qPCR analysis, RP-HPLC and gas chromatography techniques were performed to evaluate the expression of glutaminase (GLS), glutamate dehydrogenase (GDH) enzymes, concentration of metabolites; Glutamate (Glu) and alpha-ketoglutarate (α-KG) in glutaminolysis pathway, respectively. Western blotting and MTT assay were used to detect expression of mammalian target of rapamycin complex (mTORC) as signaling factor, GLS protein and cell proliferation rate, respectively.

Results

The most mRNA expression of GLS and GDH in HL-60 cells was seen at 72 h after Gal-9 treatment (p = 0.001, p = 0.0001) and in THP-1 cell line was observed at 24 h after Gal-9 addition (p = 0.001, p = 0.0001). The most mTORC and GLS protein expression in HL-60 and THP-1 cells was observed at 72 and 24 h after Gal-9 treatment (p = 0.0001), respectively. MTT assay revealed that Gal-9 could promote cell proliferation rate in both cell lines (p = 0.001). Glu concentration in HL-60 and α-KG concentration in both HL-60 (p = 0.03) and THP-1 (p = 0.0001) cell lines had a decreasing trend. But, Glu concentration had an increasing trend in THP-1 cell line (p = 0.0001).

Conclusion

Taken together, this study suggests TIM-3/Gal-9 interaction could promote glutamine metabolism in HL-60 and THP-1 cells and resulting in AML development.
Appendix
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Metadata
Title
TIM-3/Galectin-9 interaction and glutamine metabolism in AML cell lines, HL-60 and THP-1
Authors
Hooriyeh Shapourian
Mustafa Ghanadian
Nahid Eskandari
Abolfazl Shokouhi
Gülderen Yanikkaya Demirel
Alexandr V. Bazhin
Mazdak Ganjalikhani-Hakemi
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2024
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-024-11898-3

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