Small extracellular vesicles: Non-negligible vesicles in tumor progression, diagnosis, and therapy

Cancer Letters, Год журнала: 2023, Номер 580, С. 216481 - 216481

Опубликована: Ноя. 15, 2023

Small extracellular vesicles (sEVs) such as exosomes are nanoscale membranous particles (<200 nm) that have emerged crucial targets for liquid biopsy and promising drug delivery vehicles. They play a significant role in tumor progression intercellular messengers. can serve biomarkers diagnosis carriers cancer treatment. This article reviews recent studies on sEVs oncology explores their potential Following tumorigenesis, the microenvironment (TME) circulatory system undergo modifications to regulate various events TME, including angiogenesis, epithelial-mesenchymal transition (EMT), immunity, with either pro- or anti-tumor effects. been investigated use diagnostic prognostic variety of tumors, lung cancer, melanoma, breast prostate hepatocellular carcinoma. be used therapy by packaging drugs proteins into them through pre- post-isolation modification techniques. The clinical trials also summarized. Finally, challenges described possible approaches tackling suggested. Overall, will advance precision medicine has shown great applications.

Язык: Английский

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CD151-enriched migrasomes mediate hepatocellular carcinoma invasion by conditioning cancer cells and promoting angiogenesis

Journal of Experimental & Clinical Cancer Research, Год журнала: 2024, Номер 43(1)

Опубликована: Июнь 6, 2024

Abstract Background The tetraspanin family plays a pivotal role in the genesis of migrasomes, and Tetraspanin CD151 is also implicated neovascularization within tumorous contexts. Nevertheless, research pertaining to involvement hepatocellular carcinoma (HCC) its association with migrasomes remains inadequate. Methods To investigate correlation between migrasome marker TSPAN4 liver cancer, we conducted database analysis using clinical data from HCC patients. Expression levels were assessed tissues correlated patient survival outcomes. In vitro experiments performed cell lines evaluate impact expression on formation cellular invasiveness. Cell altered utilized study generation invasion capabilities. Additionally, function was explored through aggregation assays phagocytosis studies. Subsequent VEGF level tissue chip further confirmed mediating angiogenesis signal transduction. Results Our revealed significant based samples. High closely associated poor outcomes Experimentally, decreased led reduced diminished capabilities, resulting attenuated vivo metastatic potential. Migrasomes demonstrated facilitate phagocytosis, thereby promoting Furthermore, VEGF-enriched signaling angiogenesis, accelerating progression. Conclusions summary, our findings support notion that elevated promotes formation, play invasiveness cancer cells, facilitating This finding implies generated by may constitute promising high-priority target for anti-angiogenic therapy HCC, offering crucial insights in-depth exploration renewed comprehension mechanism underlying metastasis.

Язык: Английский

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Extracellular Vesicles in Breast Cancer: From Biology and Function to Clinical Diagnosis and Therapeutic Management

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(8), С. 7208 - 7208

Опубликована: Апрель 13, 2023

Breast cancer (BC) is the first worldwide most frequent in both sexes and commonly diagnosed females. Although BC mortality has been thoroughly declining over past decades, there are still considerable differences between women with early when metastatic diagnosed. treatment choice widely dependent on precise histological molecular characterization. However, recurrence or distant metastasis occurs even recent efficient therapies. Thus, a better understanding of different factors underlying tumor escape mainly mandatory. Among leading candidates continuous interplay cells their microenvironment, where extracellular vesicles play significant role. vesicles, smaller ones, also called exosomes, can carry biomolecules, such as lipids, proteins, nucleic acids, generate signal transmission through an intercellular transfer content. This mechanism allows to recruit modify adjacent systemic microenvironment support further invasion dissemination. By reciprocity, stromal use exosomes profoundly cell behavior. review intends cover literature role vesicle production normal cancerous breast tissues. Specific attention paid for diagnosis, follow-up, prognosis because actually under spotlight researchers high-potential source liquid biopsies. Extracellular new targets therapy nanovectors drive drug delivery summarized.

Язык: Английский

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Modular Calcium‐Responsive and CD9‐Targeted Phospholipase System Enhancing Endosomal Escape for DNA Delivery

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Фев. 25, 2025

Abstract Gene delivery systems must overcome multiple barriers, with endosomal escape representing a prominent obstacle. This work has previously shown that bacterial phospholipase C (PLC) enabled of non‐viral protein‐based DNA system termed TFAMoplex. Building upon this, this introduces calcium‐responsive designed to enhance through non‐covalent capturing PLC the TFAMoplex followed by its release within endosomes and nanobody‐mediated targeting membrane. approach leads improved TFAMoplexes enabling transfection HeLa cells in full serum half maximal effective concentration (EC 50 ) less than 200 ng per mL serum, using only 5 nM PLC. Particularly, modular capture, could potentially be adapted other agents constrained poor escape. These findings present promising strategy achieve efficient escape, offering prospects for macromolecules, particular nucleic acids.

Язык: Английский

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Extracellular vesicle distribution and localization in skeletal muscle at rest and following disuse atrophy

Skeletal Muscle, Год журнала: 2023, Номер 13(1)

Опубликована: Март 10, 2023

Abstract Background Skeletal muscle (SkM) is a large, secretory organ that produces and releases myokines can have autocrine, paracrine, endocrine effects. Whether extracellular vesicles (EVs) also play role in the SkM adaptive response ability to communicate with other tissues not well understood. The purpose of this study was investigate EV biogenesis factors, marker expression, localization across cell types skeletal muscle. We aimed whether concentrations are altered by disuse atrophy. Methods To identify potential markers SkM-derived EVs, EVs were isolated from rat serum using density gradient ultracentrifugation, followed fluorescence correlation spectroscopy measurements or qPCR. Single-cell RNA sequencing (scRNA-seq) data analyzed assess factor cellular tetraspanins investigated immunohistochemistry. Finally, effects mechanical unloading on expression vivo, measured nanoparticle tracking analysis both human model disuse. Results In study, we show widely used α-sarcoglycan miR-1, undetectable EVs. found including CD63, CD9, CD81, expressed variety SkM. sections showed very low detection CD81 myofibers instead accumulation within interstitial space. Furthermore, although there no differences following hindlimb suspension rats, elevated subjects after bed rest. Conclusions Our findings provide insight into distribution demonstrate importance methodological guidelines research.

Язык: Английский

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The role of Tetraspanins in digestive system tumor development: update and emerging evidence

Frontiers in Cell and Developmental Biology, Год журнала: 2024, Номер 12

Опубликована: Фев. 8, 2024

Digestive system malignancies, including cancers of the esophagus, pancreas, stomach, liver, and colorectum, are leading causes cancer-related deaths worldwide due to their high morbidity poor prognosis. The lack effective early diagnosis methods is a significant factor contributing prognosis for these malignancies. Tetraspanins (Tspans) superfamily 4-transmembrane proteins (TM4SF), classified as low-molecular-weight glycoproteins, with 33 Tspan family members identified in humans date. They interact other membrane or TM4SF form functional platform on cytoplasmic called Tspan-enriched microdomain serve multiple functions cell adhesion, migration, propagation signal transduction. In this review, we summarize various roles Tspans progression digestive tumors underlying molecular mechanisms recent years. Generally, expression CD9, CD151, Tspan1, Tspan5, Tspan8, Tspan12, Tspan15, Tspan31 upregulated, facilitating migration invasion cancer cells. Conversely, Tspan7, CD82, CD63, Tspan9 downregulated, suppressing tumor metastasis. Furthermore, connection between metastasis malignant bone reviewed. We also potential role novel immunotherapy targets an approach overcome drug resistance. Finally, discuss clinical value therapeutic treatments malignancies provide some guidance future research.

Язык: Английский

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Splicing-specific transcriptome-wide association uncovers genetic mechanisms for schizophrenia

The American Journal of Human Genetics, Год журнала: 2024, Номер 111(8), С. 1573 - 1587

Опубликована: Июнь 25, 2024

Язык: Английский

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Cargo exchange between human and bacterial extracellular vesicles in gestational tissues: a new paradigm in communication and immune development

Extracellular Vesicles and Circulating Nucleic Acids, Год журнала: 2024, Номер 5(2), С. 297 - 328

Опубликована: Июнь 18, 2024

Host-bacteria and bacteria-bacteria interactions can be facilitated by extracellular vesicles (EVs) secreted both human bacterial cells. Human EVs (BEVs) propagate transfer immunogenic cargos that may elicit immune responses in nearby or distant recipient cells/tissues. Hence, direct colonization of tissues cells is not required for stimulation. This phenomenon important the feto-maternal interface, where optimum tolerance between mother fetus a successful pregnancy. Though intrauterine cavity widely considered sterile, BEVs from diverse sources have been identified placenta amniotic cavity. These internalized cells, which help them evade host surveillance. it appears logical, whether internalize EV cargo yet to determined. However, presence placental believed trigger low-grade response primes fetal system ex-utero survival, but insufficient disrupt progression pregnancy cause intolerance adverse events. Nevertheless, exchange bioactive BEVs, mechanical underpinnings health implications such interactions, especially during pregnancy, are still understudied. Therefore, while focusing on we discussed how take up their cargo, cell (feto-maternal) inflammatory BEV stimulation, associations these with priming reproductive outcomes as preeclampsia preterm birth.

Язык: Английский

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Role of the transmembrane polar residues on CD151 in cholesterol binding

Journal of Biomolecular Structure and Dynamics, Год журнала: 2025, Номер unknown, С. 1 - 13

Опубликована: Янв. 1, 2025

Tetraspanins superfamily proteins have been shown to play an important role in several physiological processes and diseases such as cancer. Transmembrane polar residues of tetraspanins implication regulating the process cancer metastasis. Tetraspanin CD82 has demonstrated exert anti-metastatic while mutating its transmembrane domains (TMDs) abrogates metastasis inhibitory role. However, CD151, being pro-metastatic tetraspanin, TMDs CD151 cholesterol binding stability not investigated. In this study, we employed bioinformatics analysis sequences determine residue TMDs, molecular docking, dynamics, normal mode studies investigate contribution on by modelling comparing wild type with mutant CD151. The study finds three

Язык: Английский

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Calcium‐sensing receptor‐ and ADAM10‐mediated klotho shedding is regulated by tetraspanin 5

FEBS Letters, Год журнала: 2025, Номер unknown

Опубликована: Янв. 7, 2025

Soluble, circulating Klotho (sKlotho) is essential for normal health and renal function. sKlotho shed from the distal convoluted tubule (DCT), its primary source, via enzymatic cleavage. However, physiologic mechanisms that control production, trafficking, shedding are not fully defined. We previously found G protein‐coupled calcium‐sensing receptor (CaSR) co‐localizes with membrane‐bound αKlotho disintegrin/metalloprotease ADAM10 in DCT controls response to CaSR ligands pHo by activating ADAM10. Here, we advance understanding of this process showing tetraspanin 5 (Tspan5), a scaffolding chaperone protein, contributes cell surface expression specificity protein complex includes Tspan5, ADAM10, Klotho, CaSR. These results support model multiprotein complexes confer signaling beyond on processes. Impact statement Systemic determinant physiology. Studies knockout animals established role as an anti‐aging protein. The regulatory production secretion largely unknown. report Tspan CaSR‐ ADAM10‐dependent kidney, source.

Язык: Английский

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