Tumor Cell-derived Extracellular Vesicles in Modulating Phenotypes and Immune Functions of Macrophages: Mechanisms and Therapeutic Applications DOI Creative Commons

Jia-Wen Tian,

He‐Jing Zhang,

Li Siyuan

et al.

Journal of Cancer, Journal Year: 2023, Volume and Issue: 14(8), P. 1321 - 1334

Published: Jan. 1, 2023

Tumor tissues consist of tumor cells and stroma, which is structured by non-tumor the extracellular matrix.Macrophages are predominant immune in microenvironment (TME).Based on intimate interaction between macrophages cells, closely involved initiation progression, playing a key role formation, angiogenesis, metastasis, escape.Extracellular vesicles (EVs) group membrane-enclosed structures secreted almost all cell types.As crucial mediators cell-to-cell communication, EVs play various physiological processes development diseases including cancer.According to numerous studies, cell-derived (T-EVs) could highly modulate phenotypes functions macrophages, thus promoting development.Herein, we comprehensively introduce T-EVs regulating M1/M2 cytokine secretion, expression regulatory molecules membrane, phagocytosis, antigen presentation.More importantly, based effects propose several potential therapeutic approaches that may guide future attempts increase effectiveness cancer therapy.

Language: Английский

Exosomes in Cancer Progression and Therapy Resistance: Molecular Insights and Therapeutic Opportunities DOI Creative Commons
Madita Wandrey, Jadwiga Jabłońska,

Roland H. Stauber

et al.

Life, Journal Year: 2023, Volume and Issue: 13(10), P. 2033 - 2033

Published: Oct. 9, 2023

The development of therapy resistance still represents a major hurdle in treating cancers, leading to impaired treatment success and increased patient morbidity. establishment minimally invasive liquid biopsies is promising approach improving the early diagnosis, as well monitoring, solid tumors. Because their manifold functions tumor microenvironment, tumor-associated small extracellular vesicles, referred exosomes, have become subject intense research. Besides important roles cancer progression, metastasis, immune response, it has been proposed that exosomes also contribute acquisition transfer resistance, mainly by delivering functional proteins RNAs, facilitating export active drugs or functioning decoys. Extensive research focused on understanding molecular mechanisms underlying occurrence translating these into strategies for detection. With this review, we want provide an overview current knowledge about (patho-)biology state-of-the-art methods isolation analysis. Furthermore, highlight role tumorigenesis treatment, where they can function therapeutic agents, biomarkers, and/or targets. By focusing will reveal new paths exploiting diagnosis treatment.

Language: Английский

Citations

26
ITGA5 promotes tumor angiogenesis in cervical cancer DOI Creative Commons
Xiaohan Xu, Lulu Shen, Wenhan Li

et al.

Cancer Medicine, Journal Year: 2023, Volume and Issue: 12(10), P. 11983 - 11999

Published: March 31, 2023

Abstract Purpose Integrins are critical to cancer progression. Integrin alpha 5 (ITGA5) is correlated with the prognosis of cervical patients. However, whether ITGA5 plays an active role in progression or not remains unknown. Methods protein expression was detected 155 human tissues by immunohistochemistry. Data from The Cancer Genome Atlas were utilized identify risk factors for overall survival patients and ITGA5‐associated differentially expressed genes. Analyses single‐cell RNA‐seq based on Gene Expression Omnibus datasets performed show coexpression angiogenesis factors. Tube formation assay, 3D spheroid sprout qRT‐PCR, Western Blotting, ELISA, immunofluorescence conducted explore angiogenic function vitro underlying mechanisms. Results High level significantly increased terms advanced disease stage genes linked angiogenesis, immunohistochemistry showed a positive correlation between microvascular density tissues. Moreover, tumor cells transfected ITGA5‐targeting siRNA decreased ability promote endothelial tube . ITGA5/VEGFA observed cell subpopulation downregulating could be reversed VEGFA. Bioinformatics analysis highlighted PI3K‐Akt signaling pathway as downstream ITGA5. Downregulation p‐AKT VEGFA levels. Fibronectin (FN1) coated FN1‐targeting fibronectin may play ITGA5‐mediated angiogenesis. Conclusion promotes possibly potential predictive biomarker poor cancer.

Language: Английский

Citations

25
Colocalization of protein and microRNA markers reveals unique extracellular vesicle subpopulations for early cancer detection DOI Creative Commons
Zongbo Li, Kaizhu Guo, Ziting Gao

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(9)

Published: Feb. 28, 2024

Extracellular vesicles (EVs) play important roles in cell-cell communication but are highly heterogeneous, and each vesicle has dimensions smaller than 200 nm with very limited amounts of cargos encapsulated. The technique NanOstirBar (NOB)-EnabLed Single Particle Analysis (NOBEL-SPA) reported the present work permits rapid inspection single EV high confidence by confocal fluorescence microscopy, thus enables colocalization assessment for selected protein microRNA (miRNA) markers EVs produced various cell lines, or clinical sera samples. subpopulations marked unique miRNA combinations were discovered to be able detect early-stage (stage I II) breast cancer (BC). NOBEL-SPA can adapted analyze other types cargo molecules small submicron biological particles. Study sorting specific heterogeneous under different physiological conditions help discover distinct valuable examination therapeutics development gain better understanding their biogenesis.

Language: Английский

Citations

12
New roles of tumor-derived exosomes in tumor microenvironment DOI Open Access

Shiqian Chen,

Jinzhe Sun,

Huan Zhou

et al.

Chinese Journal of Cancer Research, Journal Year: 2024, Volume and Issue: 36(2), P. 151 - 166

Published: Jan. 1, 2024

Throughout tumorigenesis, the co-evolution of tumor cells and their surrounding microenvironment leads to development malignant phenotypes. Cellular communication within (TME) plays a critical role in influencing various aspects progression, including invasion metastasis. The release exosomes, type extracellular vesicle, by most cell types body, is an essential mediator intercellular communication. A growing body research indicates that tumor-derived exosomes (TDEs) significantly expedite progression through multiple mechanisms, inducing epithelial-mesenchymal transition macrophage polarization, enhancing angiogenesis, aiding immune evasion cells. Herein, we describe formation characteristics TME, summarize contents TDEs diverse functions modulating development. Furthermore, explore potential applications diagnosis treatment.

Language: Английский

Citations

12
Glycolysis Induced by METTL14 Is Essential for Macrophage Phagocytosis and Phenotype in Cervical Cancer DOI Open Access

Bingyu Wang,

Zhonghao Mao,

Jinwen Ye

et al.

The Journal of Immunology, Journal Year: 2024, Volume and Issue: 212(4), P. 723 - 736

Published: Jan. 10, 2024

Abstract N 6-methyladenosine (m6A) is the most abundant mRNA modification in mammals and it plays a vital role various biological processes. However, roles of m6A on cervical cancer tumorigenesis, especially macrophages infiltrated tumor microenvironment cancer, are still unclear. We analyzed abnormal methylation using CaSki THP-1 cell lines, that might influence macrophage polarization and/or function microenvironment. In addition, C57BL/6J BALB/c nude mice were used for validation vivo. this study, methylated RNA immunoprecipitation sequencing analysis revealed profiles cancer. Then, we discovered high expression METTL14 (methyltransferase 14, N6-adenosine-methyltransferase subunit) tissues can promote proportion programmed death protein 1 (PD-1)–positive tumor-associated macrophages, which have an obstacle to devour cells. Functionally, changes inhibit recognition phagocytosis Mechanistically, abnormality could target glycolysis tumors vivo vitro. Moreover, lactate acid produced by has important PD-1 as proinflammatory immunosuppressive mediator. effect regulated showed was potential therapeutic treating advanced human cancers.

Language: Английский

Citations

11
METTL3-mediated HSPA9 m6A modification promotes malignant transformation and inhibits cellular senescence by regulating exosomal mortalin protein in cervical cancer DOI

Keyi Ao,

Minuo Yin,

Xiaoming Lyu

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 587, P. 216658 - 216658

Published: Jan. 21, 2024

Language: Английский

Citations

10
HucMSC-Exo Induced N2 Polarization of Neutrophils: Implications for Angiogenesis and Tissue Restoration in Wound Healing DOI Creative Commons

Jiaman Yang,

Yulin Xie,

Zhikuan Xia

et al.

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 3555 - 3575

Published: April 1, 2024

Background: Neutrophils rapidly accumulate in large numbers at sites of tissue damage, exhibiting not only their well-known bactericidal capabilities but also playing crucial roles angiogenesis and repair. While exosomes derived from human umbilical cord mesenchymal stem cells (HucMSC-Exo) have emerged as a promising therapeutic tool, exact mechanisms action remain partly elusive. We hypothesize that HucMSC-Exo treatment may modulate neutrophil phenotypes, thereby significantly influencing wound healing outcomes. Methods: were isolated via ultracentrifugation subsequently administered through subcutaneous injection into full-thickness cutaneous wounds mice. To determine the impact host neutrophils on effects skin injuries, strategies including depletion adoptive transfer employed. Flow cytometry was used to evaluate proportion N2 subtype both normal diabetic wounds, effect this assessed. Furthermore, mitochondrial metabolic reprogramming driven by during polarization investigated JC1 staining, ATP quantification, fatty acid uptake assays, assessment FAO-related genes ( Cpt1b, Acadm, Acadl ). Results: Depleting strikingly dampened prohealing injury, while bone marrow rescued process. During process, some expressed markers, contrast, exhibited reduced expression markers. After with HucMSC-Exo, most increased phosphorylation STAT6, leading thus acquired an phenotype. These neutrophils, polarized boosted release proangiogenic factors, particularly BV8, myeloid cell-derived factor, induced favoring restoration. Conclusion: This research uniquely demonstrates identification injury shows could skew toward phenotype, enhancing our insight how react HucMSC-Exo. Keywords: phenotype switching, healing, restoration

Language: Английский

Citations

9
Tumor Microenvironment Modulation by Cancer-Derived Extracellular Vesicles DOI Creative Commons
Artem Ten, Vadim Kumeiko, Vladislav M. Farniev

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(8), P. 682 - 682

Published: April 15, 2024

The tumor microenvironment (TME) plays an important role in the process of tumorigenesis, regulating growth, metabolism, proliferation, and invasion cancer cells, as well contributing to resistance conventional chemoradiotherapies. Several types cells with relatively stable phenotypes have been identified within TME, including cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), neutrophils, natural killer (NK) which shown modulate cell metastasis, interaction immune system, thus promoting heterogeneity. Growing evidence suggests that tumor-cell-derived extracellular vesicles (EVs), via transfer various molecules (e.g., RNA, proteins, peptides, lipids), play a pivotal transformation normal TME into their protumorigenic counterparts. This review article focuses on functions EVs modulation view how exosomes contribute importance for diagnosis therapy.

Language: Английский

Citations

9
Innate Immune Cells in Tumour Microenvironment: A New Frontier in Cancer Immunotherapy DOI Creative Commons
Changhui Li, Xinyu Yu, Xinyan Han

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(9), P. 110750 - 110750

Published: Aug. 17, 2024

Innate immune cells, crucial in resisting infections and initiating adaptive immunity, play diverse significant roles tumor development. These including macrophages, granulocytes, dendritic cells (DCs), innate lymphoid innate-like T are pivotal the microenvironment (TME). components of TME, based on which various immunotherapy strategies have been explored. Immunotherapy strategies, such as novel checkpoint inhibitors, STING/CD40 agonists, macrophage-based surface backpack anchoring,

Language: Английский

Citations

9
Fructose-1,6-bisphosphatase 1 in cancer: Dual roles, mechanistic insights, and therapeutic potential – A comprehensive review DOI

Qinghang Song,

Jiehe Sui,

Yuxuan Yang

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 139273 - 139273

Published: Jan. 1, 2025

Language: Английский

Citations

1