Metformin impacts the differentiation of mouse bone marrow cells into macrophages affecting tumour immunity

被引:4
作者
Scafidi, Andrea [1 ,2 ]
Mogensen, Frida Lind-Holm [1 ,2 ]
Campus, Eleonora [1 ,2 ]
Pailas, Alexandros [2 ,3 ]
Neumann, Katrin [3 ]
Legrave, Nathalie [4 ]
Bernardin, Francois [4 ,5 ]
Pereira, Sandro L. [4 ,5 ]
Antony, Paul M. A. [6 ]
Nicot, Nathalie [7 ,8 ]
Mittelbronn, Michel [9 ,10 ,11 ,12 ,13 ]
Grunewald, Anne [5 ]
Nazarov, Petr, V [14 ,15 ]
Poli, Aurelie [1 ]
Van Dyck, Eric [3 ]
Michelucci, Alessandro [1 ]
机构
[1] Luxembourg Inst Hlth, Dept Canc Res, Neuroimmunol Grp, L-1210 Luxembourg, Luxembourg
[2] Univ Luxembourg, Fac Sci Technol & Med, L-4365 Esch Sur Alzette, Luxembourg
[3] Luxembourg Inst Hlth, Dept Canc Res, DNA Repair & Chemoresistance, L-1210 Luxembourg, Luxembourg
[4] Luxembourg Inst Hlth, Dept Canc Res, Metabol Platform, L-1445 Strassen, Luxembourg
[5] Univ Luxembourg, Luxembourg Ctr Syst Biomed, Mol & Funct Neurobiol Grp, L-4362 Esch Sur Alzette, Luxembourg
[6] Univ Luxembourg, Luxembourg Ctr Syst Biomed, Bioimaging Platform, L-4362 Esch Sur Alzette, Luxembourg
[7] Luxembourg Inst Hlth, LuxGen Genome Ctr, L-3555 Dudelange, Luxembourg
[8] Lab Natl Sante, L-3555 Dudelange, Luxembourg
[9] Univ Luxembourg, Fac Sci Technol & Med, Dept Life Sci & Med, L-4367 Belvaux, Luxembourg
[10] Univ Luxembourg, Luxembourg Ctr Syst Biomed, L-4362 Esch Sur Alzette, Luxembourg
[11] Luxembourg Inst Hlth, Dept Canc Res, L-1210 Luxembourg, Luxembourg
[12] Luxembourg Ctr Neuropathol, Lab Natl Sante, L-3555 Dudelange, Luxembourg
[13] Natl Ctr Pathol, Lab Natl Sante, L-3555 Dudelange, Luxembourg
[14] Luxembourg Inst Hlth, Dept Med Informat, Bioinformat & AI Unit, L-1445 Strassen, Luxembourg
[15] Luxembourg Inst Hlth, Dept Canc Res, Multi Data Sci Res Grp, L-1445 Strassen, Luxembourg
关键词
Luxembourg; Metformin; Macrophages; Phagocytosis; Anti-tumour; HIF1; alpha; Glycolysis; UP-REGULATION; HYPOXIA; POLARIZATION; ACTIVATION; PATHWAY; GENES;
D O I
10.1016/j.heliyon.2024.e37792
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: Epidemiological studies suggest that metformin reduces the risk of developing several types of cancer, including gliomas, and improves the overall survival in cancer patients. Nevertheless, while the effect of metformin on cancer cells has been extensively studied, its impact on other components of the tumour microenvironment, such as macrophages, is less understood. Results: Metformin-treated mouse bone marrow cells differentiate into spindle-shaped macrophages exhibiting increased phagocytic activity and tumour cell cytotoxicity coupled with modulated expression of co-stimulatory molecules displaying reduced sensitivity to inflammatory cues compared with untreated cells. Transcriptional analyses of metformin-treated mouse bone marrow-derived macrophages show decreased expression levels of pro-tumour genes, including Tgfbi and Il1 beta, related to enhanced mTOR/HIF1 alpha signalling and metabolic rewiring towards glycolysis. Significance: Our study provides novel insights into the immunomodulatory properties of metformin in macrophages and its potential application in preventing tumour onset and in cancer immunotherapy.
引用
收藏
页数:17
相关论文
共 82 条
[1]   Cancer-inducing niche: the force of chronic inflammation [J].
Afify, Said M. ;
Hassan, Ghmkin ;
Seno, Akimasa ;
Seno, Masaharu .
BRITISH JOURNAL OF CANCER, 2022, 127 (02) :193-201
[2]   Differential Expression of Human Peripheral Mononuclear Cells Phenotype Markers in Type 2 Diabetic Patients and Type 2 Diabetic Patients on Metformin [J].
Al Dubayee, Mohammed S. ;
Alayed, Hind ;
Almansour, Rana ;
Alqaoud, Nora ;
Alnamlah, Rahaf ;
Obeid, Dana ;
Alshahrani, Awad ;
Zahra, Mahmoud M. ;
Nasr, Amre ;
Al-Bawab, Ahmad ;
Aljada, Ahmad .
FRONTIERS IN ENDOCRINOLOGY, 2018, 9
[3]   Regulation of Autophagy by Protein Kinase C-ε in Breast Cancer Cells [J].
Basu, Alakananda .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (12) :1-11
[4]   Enteric neurons from Parkinson's disease patients display ex vivo aberrations in mitochondrial structure [J].
Baumuratov, A. S. ;
Antony, P. M. A. ;
Ostaszewski, M. ;
He, F. ;
Salamanca, L. ;
Antunes, L. ;
Weber, J. ;
Longhino, L. ;
Derkinderen, P. ;
Koopman, W. J. H. ;
Diederich, N. J. .
SCIENTIFIC REPORTS, 2016, 6
[5]   Classification of M1/M2-polarized human macrophages by label-free hyperspectral reflectance confocal microscopy and multivariate analysis [J].
Bertani, Francesca R. ;
Mozetic, Pamela ;
Fioramonti, Marco ;
Iuliani, Michele ;
Ribelli, Giulia ;
Pantano, Francesco ;
Santini, Daniele ;
Tonini, Giuseppe ;
Trombetta, Marcella ;
Businaro, Luca ;
Selci, Stefano ;
Rainer, Alberto .
SCIENTIFIC REPORTS, 2017, 7
[6]   A temporal perspective for tumor-associated macrophage identities and functions [J].
Bleriot, Camille ;
Dunsmore, Garett ;
Alonso-Curbelo, Direna ;
Ginhoux, Florent .
CANCER CELL, 2024, 42 (05) :747-758
[7]   The malate-aspartate shuttle (Borst cycle): How it started and developed into a major metabolic pathway [J].
Borst, Piet .
IUBMB LIFE, 2020, 72 (11) :2241-2259
[8]   GlioVis data portal for visualization and analysis of brain tumor expression datasets [J].
Bowman, Robert L. ;
Wang, Qianghu ;
Carro, Angel ;
Verhaak, Roel G. W. ;
Squatrito, Massimo .
NEURO-ONCOLOGY, 2017, 19 (01) :139-141
[9]   Effects of glycolysis on the polarization and function of tumor-associated macrophages (Review) [J].
Cao, Jiaying ;
Zeng, Feng ;
Liao, Shan ;
Cao, Lan ;
Zhou, Yanhong .
INTERNATIONAL JOURNAL OF ONCOLOGY, 2023, 62 (06)
[10]   Much more than M1 and M2 macrophages, there are also CD169+ and TCR+ macrophages [J].
Chavez-Galan, Leslie ;
Olleros, Maria L. ;
Vesin, Dominique ;
Garcia, Irene .
FRONTIERS IN IMMUNOLOGY, 2015, 6