التفاصيل البيبلوغرافية
| العنوان: |
PD-L1 stimulation can promote proliferation and survival of leukemic cells by influencing glucose and fatty acid metabolism in acute myeloid leukemia |
| المؤلفون: |
Mojdeh Soltani, Mustafa Ghanadian, Behrooz Ghezelbash, Abolfazl Shokouhi, Andrey A. Zamyatnin, Alexandr V. Bazhin, Mazdak Ganjalikhani-Hakemi |
| المصدر: |
BMC Cancer, Vol 23, Iss 1, Pp 1-9 (2023) |
| بيانات النشر: |
BMC, 2023. |
| سنة النشر: |
2023 |
| المجموعة: |
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: |
Acute myeloid leukemia, AML, Fatty acid oxidation, Immunometabolism, Pentose phosphate pathway, Programmed death ligand-1, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: |
Abstract Background Leukemic cell metabolism plays significant roles in their proliferation and survival. These metabolic adaptations are under regulation by different factors. Programmed Death Ligand -1 (CD-274) is one of the immune checkpoint ligands that do not only cause the immune escape of cancer cells, but also have some intracellular effects in these cells. PD-L1 is overexpressed on leukemic stem cells and relates with poor prognosis of AML. In this study, we investigated effects of PD-L1 stimulation on critical metabolic pathways of glucose and fatty acid metabolisms that have important roles in proliferation and survival of leukemic cells. Methods After confirmation of PD-L1 expression by flow cytometry assay, we used recombinant protein PD-1 for stimulation of the PD-L1 on two AML cell lines, HL-60 and THP-1. Then we examined the effect of PD-L1 stimulation on glucose and fatty acid metabolism in cells at the genomic and metabolomic levels in a time dependent manner. We investigated expression changes of rate limiting enzymes of theses metabolic pathways (G6PD, HK-2, CPT1A, ATGL1 and ACC1) by qRT-PCR and also the relative abundance changes of free fatty acids of medium by GC. Results We identified a correlation between PD-L1 stimulation and both fatty acid and glucose metabolism. The PD-L1 stimulated cells showed an influence in the pentose phosphate pathway and glycolysis by increasing expression of G6PD and HK-2 (P value = 0.0001). Furthermore, PD-L1 promoted fatty acid β-oxidation by increasing expression of CPT1A (P value = 0.0001), however, their fatty acid synthesis was decreased by reduction of ACC1 expression (P value = 0.0001). Conclusion We found that PD-L1 can promote proliferation and survival of AML stem cells probably through some metabolic changes in leukemic cells. Pentose phosphate pathway that has a critical role in cell proliferation and fatty acids β-oxidation that promote cell survival, both are increased by PD-L1 stimulation on AML cells. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
1471-2407 |
| Relation: |
https://doaj.org/toc/1471-2407 |
| DOI: |
10.1186/s12885-023-10947-7 |
| URL الوصول: |
https://doaj.org/article/c1297f0c3500416791b9801fdb1275b4 |
| رقم الانضمام: |
edsdoj.1297f0c3500416791b9801fdb1275b4 |
| قاعدة البيانات: |
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