Cell Reports, Год журнала: 2025, Номер 44(3), С. 115432 - 115432
Опубликована: Март 1, 2025
Язык: Английский
Molecular Cell, Год журнала: 2023, Номер 84(1), С. 23 - 33
Опубликована: Ноя. 28, 2023
Язык: Английский
Процитировано
47
Journal of Clinical Investigation, Год журнала: 2024, Номер 134(2)
Опубликована: Янв. 15, 2024
Immunometabolism is a burgeoning field of research that investigates how immune cells harness nutrients to drive their growth and functions. Myeloid play pivotal role in tumor biology, yet metabolic influence on antitumor responses remains inadequately understood. This Review explores the landscape tumor-associated macrophages, including immunoregulatory roles glucose, fatty acids, glutamine, arginine, alongside tools used perturb metabolism promote immunity. The confounding inhibitors our interpretation myeloid phenotypes will also be discussed. A binary schema currently describe macrophage immunological phenotypes, characterizing inflammatory M1 as supported by glycolysis, immunosuppressive M2 oxidative phosphorylation. However, this classification likely underestimates variety states vivo. Understanding these nuances critical when developing interventional strategies. Future should focus refining drug specificity targeted delivery methods maximize therapeutic efficacy.
Язык: Английский
Процитировано
17
Cell Reports, Год журнала: 2025, Номер 44(1), С. 115130 - 115130
Опубликована: Янв. 1, 2025
Highlights•SLC7A5 is required for proliferation under arginine-free conditions when citrulline present•SLC7A5 loss impairs arginine metabolism•Small-molecule inhibitors of SLC7A5 can be paired with senolytic drugs to drive apoptosis•SLC7A5 knockout decreases import in a xenograft modelSummaryTumor cells must optimize metabolite acquisition between synthesis and uptake from microenvironment characterized by hypoxia, lactate accumulation, depletion many amino acids, including arginine. We performed metabolism-focused functional screen using CRISPR-Cas9 identify pathways factors that enable tumor growth an arginine-depleted environment. Our identified the SLC-family transporter as growth, we hypothesized this protein functions high-affinity transporter. Using isotope tracing experiments, show metabolism into are dependent upon expression SLC7A5. Pharmacological inhibition blocks low-arginine across diverse group cancer cell lines. Loss reduces mouse model. conditionally essential role metabolism, propose SLC7A5-targeting therapeutic strategies may effective context limitation.Graphical abstract
Язык: Английский
Процитировано
1
The EMBO Journal, Год журнала: 2025, Номер unknown
Опубликована: Фев. 7, 2025
Abstract L-arginine is the most nitrogen-rich amino acid, acting as a key precursor for synthesis of nitrogen-containing metabolites and an essential intermediate in clearance excess nitrogen. Arginine’s side chain possesses guanidino group which has unique biochemical properties, plays primary role nitrogen excretion (urea), cellular signaling (nitric oxide) energy buffering (phosphocreatine). The post-translational modification protein-incorporated arginine by guanidino-group methylation also contributes to epigenetic gene control. Most human cells do not synthesize sufficient meet demand are dependent on exogenous arginine. Thus, dietary important maintaining health, particularly upon physiologic stress. How adapt changes extracellular availability unclear, mostly because nearly all tissue culture media supplemented with supraphysiologic levels Evidence emerging that arginine-deficiency can influence disease progression. Here, we review new insights into importance metabolite, emphasizing central mitochondria synthesis/catabolism recent discovery act molecule regulating expression organelle dynamics.
Язык: Английский
Процитировано
1
eLife, Год журнала: 2024, Номер 13
Опубликована: Фев. 13, 2024
The tumor microenvironment is a determinant of cancer progression and therapeutic efficacy, with nutrient availability playing an important role. Although it established that the local abundance specific nutrients defines metabolic parameters for growth, factors guiding in compared to normal tissue blood remain poorly understood. To define these renal cell carcinoma (RCC), we performed quantitative metabolomic comprehensive lipidomic analyses interstitial fluid (TIF), adjacent kidney (KIF), plasma samples collected from patients. TIF composition closely resembles KIF, suggesting tissue-specific unrelated presence exert stronger influence on levels than tumor-driven alterations. Notably, select metabolite changes consistent known features RCC metabolism are found TIF, while glucose not depleted lower those KIF. These findings inform dynamics RCC, highlighting dominant role non-cancer-driven shaping tumors.
Язык: Английский
Процитировано
7
Analytical Science Advances, Год журнала: 2024, Номер 5(5-6)
Опубликована: Июнь 1, 2024
Abstract The field of metabolomics has gained tremendous interest in recent years. Whether the goal is to discover biomarkers related certain pathologies or better understand impact a drug contaminant, numerous studies have demonstrated how crucial it variations metabolism. Detailed knowledge metabolic variabilities can lead more effective treatments, as well faster less invasive diagnostics. Exploratory approaches are often employed metabolomics, using relative quantitation look at perturbations between groups samples. Most been based on metabolite profiling quantitation, with very few an approach for absolute quantitation. Using accurate facilitates comparison different studies, enabling longitudinal studies. In this review, we discuss most widely used techniques quantitative mass spectrometry (MS). Various aspects will be addressed, such use external and/or internal standards, derivatization techniques, vivo isotopic labelling, MS imaging. principles, associated limitations and challenges, described each approach.
Язык: Английский
Процитировано
6
Current Opinion in Biotechnology, Год журнала: 2023, Номер 83, С. 102970 - 102970
Опубликована: Июль 24, 2023
The tumor microenvironment (TME) plays a crucial role in regulating the state and function of all cell types residing thus impacts many aspects biology. importance TME has led to an interest characterizing composition how components regulate cancer stromal Tumor interstitial fluid (TIF) is local perfusate that carries metabolites, electrolytes, soluble macromolecules tumor-resident cells. Recently, techniques isolate TIF have been coupled with analytical interrogate TIF, providing new insight into composition. In this review, we will discuss what studies indicate about avenues analysis provides delineate regulates
Язык: Английский
Процитировано
14
Disease Models & Mechanisms, Год журнала: 2024, Номер 17(9)
Опубликована: Сен. 1, 2024
ABSTRACT Cancer cells require a constant supply of lipids. Lipids are diverse class hydrophobic molecules that essential for cellular homeostasis, growth and survival, energy production. How tumors acquire lipids is under intensive investigation, as these mechanisms could provide attractive therapeutic targets cancer. Cellular lipid metabolism tightly regulated responsive to environmental stimuli. Thus, in cancer heavily influenced by the tumor microenvironment. In this Review, we outline which microenvironment determines metabolic pathways used We also discuss emerging literature reveals availability influences many cancers, including those not traditionally associated with biology. changes instigated have ‘ripple’ effects throughout densely interconnected network cells. Given interconnectedness metabolism, new tools approaches identify requirements characterize how influence other aspects metabolism.
Язык: Английский
Процитировано
5
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Июнь 12, 2024
Abstract Nutrient stress represents a significant barrier for antitumor immunity, and tumor interstitial fluid (TIF) often contains metabolites that hinder immune function. However, it is difficult to isolate the effects of nutrient from other suppressive factors. Thus, we employed chemically-defined cell culture medium based on metabolomic profile TIF: Tumor Interstitial Fluid Medium (TIFM). Culture CD8 + T cells in TIFM limited expansion impaired effector functions upon restimulation, suggesting alone sufficient drive dysfunction. We identified phosphoethanolamine (pEtn), phospholipid intermediate, as driver pEtn dampened TCR signaling by depleting diacylglycerol required signal transduction. Reduction accumulation tumors improved intratumoral function control, plays dominant role TME immunosuppression.
Язык: Английский
Процитировано
4
Science Advances, Год журнала: 2024, Номер 10(40)
Опубликована: Окт. 2, 2024
Solid tumors are characterized by dysfunctional vasculature that limits perfusion and delivery of nutrients to the tumor microenvironment. Limited coupled with high metabolic demand growing has led hypothesis many experience stress driven limited availability such as glucose, oxygen, amino acids in tumor. Such important implications for biology cells microenvironment, affecting both disease progression response therapies. Recently, techniques have been developed identify limiting resulting stresses solid tumors. These greatly expanded our understanding limitations This review will discuss these experimental tools emerging picture arising from recent studies using approaches.
Язык: Английский
Процитировано
4