Cell Communication and Signaling最新文献

{"title":"Therapeutic potential of BOLD-100, a GRP78 inhibitor, enhanced by ATR inhibition in pancreatic ductal adenocarcinoma.","authors":"Su In Lee, Ah-Rong Nam, Kyoung-Seok Oh, Jae-Min Kim, Ju-Hee Bang, Yoojin Jeong, Sea Young Choo, Hyo Jung Kim, Jeesun Yoon, Tae-Yong Kim, Do-Youn Oh","doi":"10.1186/s12964-025-02242-8","DOIUrl":"10.1186/s12964-025-02242-8","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is characterized by poor prognosis and resistance to conventional therapies, necessitating novel treatments. The high proliferative rate and protein synthesis in PDAC induce endoplasmic reticulum (ER) stress, with Glucose-Regulated Protein 78 (GRP78), a key regulator of ER stress and the Unfolded Protein Response (UPR), playing a pivotal role in PDAC progression. Despite its relevance, GRP78-targeted therapies remain unexplored in PDAC. BOLD-100, a novel GRP78 inhibitor, presents a potential therapeutic approach by disrupting GRP78 transcription, though its effects on PDAC have yet to be fully elucidated. Here, we found that BOLD-100 induces PDAC cell death through the UPR pathway activation, leading to CHOP-dependent apoptosis. BOLD-100 generates reactive oxygen species (ROS), inducing R-loop formation that triggers a DNA damage response via the ATR/Chk1 axis. BOLD-100 synergizes with AZD6738, an ATR inhibitor, to enhance anti-tumor efficacy compared to either agent alone in both in vitro and in vivo models. These findings suggest that BOLD-100, especially in combination with an ATR inhibitor, represents a promising therapeutic option for patients with PDAC.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"281"},"PeriodicalIF":8.2,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic analysis of hydrogen peroxide-treated human chondrocytes shows endoplasmic reticulum stress, cytoskeleton remodeling, and altered secretome composition.","authors":"Thais Mingatos de Toledo, Hellen Paula Valerio, Amanda Teixeira de Melo, Renata Nascimento Gomes, Thatiana Corrêa de Melo, Marcus Vinicius Buri, Marcelo Medina de Souza, Deivid Martins Santos, Hugo Vigerelli, Miryam Paola Alvarez Flores, Giuseppe Palmisano, Ana Marisa Chudzinski-Tavassi","doi":"10.1186/s12964-025-02291-z","DOIUrl":"10.1186/s12964-025-02291-z","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Chondrocyte homeostasis is vital for maintaining the extracellular matrix (ECM) and overall cartilage health. In osteoarthritis (OA), for example, oxidative stress resulting from redox imbalances can disrupt chondrocyte homeostasis, leading to cartilage degradation. Hydrogen peroxide (H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt;), a reactive oxygen species (ROS), is a key mediator of oxidative stress and contributes to chondrocyte apoptosis and ECM degradation. Previous studies have explored individual protein responses to oxidative stress; however, a comprehensive proteomic analysis in chondrocytes has not been conducted. In this study, we aimed to assess the global proteomic alterations in chondrocytes exposed to H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt; using a shotgun proteomics approach, which enables the detection of a broad spectrum of proteomic changes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Chondrocytes were treated with H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt; for 1, 4, and 16 h followed by protein extraction and processing, including denaturation, alkylation, and trypsin digestion. The peptides were then acidified, desalted, dried, and resuspended for LC-MS/MS. Proteomics data were analyzed using MaxQuant software to identify and quantify proteins. Secretome analysis was performed to examine protein secretion changes under oxidative stress. The statistical significance of all proteomics and secretome data was assessed using a two-tailed Student's t-test with a permutation-based FDR and an S0 parameter of 0.1 in the Perseus software. Other methods, including quantitative PCR, western blotting, and immunofluorescence, were employed to complement the proteomic analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Our findings revealed that oxidative stress primarily affected the endoplasmic reticulum (ER), causing notable alterations in the expression of ER-associated proteins, redox-responsive enzymes, chaperones, and sialyltransferases. These changes increased intracellular accumulation of ECM proteins and decreased secretion into the extracellular environment, indicating impaired protein trafficking and secretion. Additionally, immune-related pathways were activated in the long term, with a short-term upregulation of inflammatory markers, such as interleukin (IL)-6 and IL-18, although the levels of matrix metalloproteinases (MMPs) remained stable, indicating that not only complex inflammatory stimuli, but also oxidative stress responses can disrupt ECM homeostasis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Our study demonstrates a detailed proteomic view of the stress response of H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2-&lt;/sub&gt;treated chondrocytes, highlighting the significant changes in ER function, cytoskeletal remodeling, protein secretion, and immune responses. These changes suggest that oxidative stress impacts ECM balance and can contribute to cartilage disorders, such as OA, through different mechanisms than what is usually observed with inflammatory stimulus, offering new insights into t","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"282"},"PeriodicalIF":8.2,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic changes and serotype-specific responses of alveolar type II epithelial cells to Streptococcus pneumoniae in resolving influenza A virus infection.","authors":"Julia D Boehme, Andreas Jeron, Kristin Schultz, Lars Melcher, Katharina Schott, Elif Gelmez, Andrea Kröger, Sabine Stegemann-Koniszewski, Dunja Bruder","doi":"10.1186/s12964-025-02284-y","DOIUrl":"10.1186/s12964-025-02284-y","url":null,"abstract":"<p><strong>Background: </strong>Pneumococcal pneumonia following influenza A virus (IAV) infection is a synergistic complication with high mortality in which IAV infection modulates host antibacterial responses and affects bacterial invasiveness of Streptococcus pneumoniae (S. pn.). IAV-mediated effects can last beyond viral clearance. In acute IAV pneumonia, alveolar type II epithelial cells (AECII) are primary targets for viral replication and contribute to the immune response. Our study addresses sustained effects of IAV infection on AECII and consequences for their response towards different serotypes of S. pn.</p><p><strong>Methods: </strong>We analyzed bacterial loads, respiratory inflammation and AECII gene transcription profiling in mice infected with IAV and/or one of three S. pn. serotypes of varying invasiveness (4 > 7F > 19F). We inferred a scale-free-like ARACNE gene co-expression network on AECII transcriptional regulation under these conditions. We performed Western blotting for protein expression of interferon signaling components in AECII. We additionally performed ATAC-seq analysis of AECII isolated 14 days following IAV infection.</p><p><strong>Results: </strong>Previous IAV infection rendered the lung susceptible to invasive S. pn. infection with serotype 4 and the mildly invasive 7F but not 19F. Particularly secondary infection with 7F induced exacerbated inflammatory responses as compared to bacterial infection alone, marked by increased protein expression of type I and II interferons. AECII gene co-expression network revealed interferon-response network modules. Network-mapping unfolded S. pn. serotype-specific transcriptional network responses/usage and secondary S. pn. infection was found to abrogate an IAV-induced AECII proliferative configuration. Enhanced expression of several ARACNE network genes were found to be associated with increased chromatin accessibility at their promoter regions.</p><p><strong>Conclusions: </strong>Our study demonstrates AECII to retain a sustained IAV-associated configuration with epigenetic involvement, affecting their proliferation and serotype-specifically intensifying their transcriptional response, mainly to interferons, in secondary S. pn.</p><p><strong>Infection: </strong>In a broader context, our results suggest the concepts of peripheral inflammatory imprinting and trained innate immunity to apply to cells of the respiratory epithelium in the context of subsequent viral/bacterial challenges.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"278"},"PeriodicalIF":8.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144287161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intramyocardial injection of pre-cultured endothelial progenitor cells and mesenchymal stem cells inside alginate/gelatin microspheres induced angiogenesis in infarcted rabbits.","authors":"Hassan Amini, Çığır Biray Avci, Sajed Nazif Kerdar, Ayla Hassani, Meisam Amini, Narges Mardi, Sepideh Saghati, Maryam Taghavi Narmi, Leila Sabour Takanlou, Maryam Sabour Takanlou, Ali Baradar Khoshfetrat, Mohammad Nori, Shahriar Hashemzadeh, Reza Rahbarghazi","doi":"10.1186/s12964-025-02301-0","DOIUrl":"10.1186/s12964-025-02301-0","url":null,"abstract":"","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"279"},"PeriodicalIF":8.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144287162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dis3l2 is essential for neural crest survival by modulating Akt signaling.","authors":"Sian D'Silva, Tuhina Prasad, Megha Kumar","doi":"10.1186/s12964-025-02288-8","DOIUrl":"10.1186/s12964-025-02288-8","url":null,"abstract":"<p><p>DIS3-like 3'-5' exoribonuclease 2 (DIS3L2), an exoribonuclease, is known to preferentially degrade uridylated RNA substrates, miRNAs, and ncRNAs. Recent reports show that DIS3L2 also plays a key role in cell proliferation and tumor growth. Mutations in DIS3L2 are associated with congenital overgrowth disorders such as Perlman syndrome, yet the developmental functions of DIS3L2 remain unknown. We report the developmental role of dis3l2 in neural crest specification, patterning, and survival in the zebrafish embryo. The dis3l2 morphants exhibited reduced expression of neural crest specifier genes coupled with extensive apoptosis in the neural tissue. Our study demonstrates that dis3l2 regulates neural tissue apoptosis and progenitor functions through the Akt-GSK3β signaling pathway. Additionally, we show that dis3l2 is essential for early mitoses in the zebrafish blastula and plays a key role in maintaining spindle length at metaphase, chromosome congression, spindle pole integrity, and cytokinesis. In summary, we identify new functions of exoribonuclease dis3l2 in cell fate specification, neural crest survival, and mitosis during embryogenesis, which form the underlying basis of DIS3L2-associated Perlman syndrome.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"277"},"PeriodicalIF":8.2,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles as missiles for enhanced anti-tumor efficacy of oncolytic viruses: from disseminating oncolysis and anti-tumor immunity to targeted delivery.","authors":"Mehrnoush Safarzadeh, Nastaran Saadat, Sara Abbasi-Molaei, Mohsen Rastegari-Pouyani","doi":"10.1186/s12964-025-02283-z","DOIUrl":"10.1186/s12964-025-02283-z","url":null,"abstract":"<p><p>Oncolytic viruses (OVs) have been introduced as a promising anti-cancer platform capable of selectively killing cancer cells (oncolysis) without causing damage to normal cells. These viruses also stimulate the innate and adaptive immune responses and can remodel the tumor microenvironment (TME) in favor of anti-tumor immunity. Still, successful and efficient OV application in the clinical settings encounters several challenges including immune mediated clearance and low tumor tissue targeting. Extracellular vesicles (EVs) have emerged as a useful vehicle for efficient and selective delivery of various therapeutics including chemotherapy drugs, nucleic acid-based anti-cancer agents and immunostimulatory molecules into the TME. EVs can also be employed as a proper vehicle to enhance OVs tumor-selective delivery and protect them from the host immune system mediated removal following systemic administration as a key hurdle on the way of an efficacious oncolytic virotherapy. OVs can also take advantage of EVs to spread their oncolytic activity to metastatic sites distant from the primary tumor as well as instigate robust anti-tumor immune responses. In this paper, we have tried to review the current literature regarding the roles and applications of EVs in cancer OV therapy and provide a conclusion on future directions and application of this novel technology.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"276"},"PeriodicalIF":8.2,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA polymerase II subunit 5-mediating protein limits TLR4-induced innate immune activation in macrophages by inhibiting IKKβ/NF-κB signaling during sepsis.","authors":"Shu-Jie Pang, Tian-Yi Jiang, Nai-Guo Wang, Xiao-Wen Cui, Hui Wang, Yu-Fei Pan, Ning Yang, Li-Wei Dong","doi":"10.1186/s12964-025-02278-w","DOIUrl":"10.1186/s12964-025-02278-w","url":null,"abstract":"<p><strong>Background: </strong>Nuclear factor κB (NF-κB) activity is a central component of inflammatory and innate immune responses, which plays a crucial role in sepsis. The inhibition of NF-κB signaling and the IκB kinase (IKK) complex is important for understanding the control of innate immunity and regulating the progress of sepsis.</p><p><strong>Methods: </strong>We constructed transgenic mouse strains (Rmp^f/f; Lyz2-Cre⁺), and then established lipopolysaccharide (LPS), cecal ligation and perforation (CLP)-induced sepsis models. Hematoxylin-eosin (HE) staining, ELISA, and flow cytometry assay were employed to evaluate the sepsis-related damage and the activation of the inflammatory-related signaling pathway. In vitro, differential expression of RMP cell lines and primary macrophage isolated from transgenic mice were utilized to assess the activation of the NF-κB signaling pathway by Western blot (WB), reverse transcription-polymerase chain reaction (RT-PCR), and ELISA tests. Co‑immunoprecipitation (Co-IP), WB, GST-pulldown, phosphorylation mass spectrometry, surface plasmon resonance (SPR), and IKK activity detection assay were employed to investigate the underlying molecular mechanism by which RMP restrains IKK-NF-κB pathway.</p><p><strong>Results: </strong>We identified RNA polymerase II subunit 5 (RPB5)-mediating protein (RMP) as an inhibitor of the IKK complex, which thus inhibited NF-κB signaling in macrophages. In resting macrophages, RMP was directly bound to the kinase domain of IKKβ and inhibited its activity by recruiting protein phosphatase 2 A (PP2A) to the IKK complex. When mouse macrophages were treated with LPS, a Toll-like receptor 4 (TLR4) agonist that stimulates NF-κB signaling, RMP was phosphorylated by IKKβ at Ser⁴³⁹ and dissociated from the IKK complex, which further activated NF-κB signaling. Macrophage-specific deletion of Rmp reduced survival in mice due to an increased inflammatory response in experimental models of sepsis.</p><p><strong>Conclusions: </strong>RMP inhibits TLR4-induced NF-κB activation and exerts homeostatic control of innate immunity, and may be promising as a therapeutic target in the limiting of NF-κB signaling and attenuating sepsis-related damage.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"274"},"PeriodicalIF":8.2,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myometrial extracellular vesicles promoted endometrial mesenchymal stem/stromal cells to self-renewal via jag1-mediated notch signaling.","authors":"Sisi Zhang, Ernest H Y Ng, William S B Yeung, Rachel W S Chan","doi":"10.1186/s12964-025-02282-0","DOIUrl":"10.1186/s12964-025-02282-0","url":null,"abstract":"<p><strong>Background: </strong>In the human endometrium, studies show the importance of extracellular vesicles in mediating various physiological as well as pathological processes. We have demonstrated that the myometrial cells are candidate niche cells of the endometrial mesenchymal stem/stromal cells (eMSC) modulating their biological function. The Notch signaling pathway regulates the endometrial stem cell functions. Although classical Notch signaling relies on direct cell contract for actions, this pathway can also be activated at a distance by Notch ligands containing extracellular vesicles (EV). We hypothesized that certain Notch ligand(s) are packaged into the myometrial EV to mediate stem cell functions.</p><p><strong>Methods: </strong>Endometrial samples were obtained from women undergoing total abdominal hysterectomy. Endometrial MSC (CD140b⁺CD146⁺ cells) were cocultured with myometrial EV and the percentage of eMSC was analysed by flow cytometry. Blockage of the secretion of EV was performed by transfection of RAB27 A siRNA. Western blot analysis and gene silencing approach were used to validate the role of Notch signaling in eMSC. The therapeutic features of transplanted eMSC/myometrial EV was determined using a mouse injured endometrium model.</p><p><strong>Results: </strong>EV released from myometrial cells could be internalized by eMSC, leading to a significant stimulatory effect on the self-renewal and clonogenic activity of eMSC. Pharmacological inhibition of Notch signaling with DAPT or silencing of NOTCH 1 nullified the stimulatory effects. Myometrial EV contains a high amount of the Notch ligand - JAG1, thus inducing a strong Notch activity in eMSC. When JAG1 was silenced in the myometrial EV, the self-renewal and clonogenic activity was reduced. Combined transplantation of eMSC with myometrial EV improves the therapeutic effect of eMSC in endometrial regeneration in vivo. The observed therapeutic feature was potentially achieved by elevating the cell proliferation and suppressing apoptosis in the injured mouse endometrium.</p><p><strong>Conclusions: </strong>This study identifies a novel EV mediated communication axis between the myometrial cells and the eMSC, providing new insights into endometrial regeneration. The findings highlight the potential of eMSC and myometrial EV as a therapeutic strategy for women with intrauterine adhesions and other endometrial disorders.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"275"},"PeriodicalIF":8.2,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemotherapy reprograms miRNA expression profiles in apoptotic extracellular vesicles from medulloblastoma cells, regulating pro- and anti-proliferative effects on recipient drug-naïve cells.","authors":"Rosa Mistica C Ignacio, Helen Forgham, Zerong Ma, Anya Jensen, George Sharbeen, Juanfang Ruan, David S Ziegler, Maria Tsoli, Phoebe A Phillips, Chelsea Mayoh, Maria Kavallaris, Joshua McCarroll","doi":"10.1186/s12964-025-02241-9","DOIUrl":"10.1186/s12964-025-02241-9","url":null,"abstract":"<p><strong>Background: </strong>Extracellular vesicles (EVs) play a crucial role in intercellular communication. While the effects of EVs released from living or non-dying cancer cells are well characterized, the impact of EVs released from chemotherapy-treated or apoptotic cancer cells is less understood. This study investigated the effects of the chemotherapy agent cisplatin on EV release and miRNA content in apoptotic medulloblastoma cells, as well as their influence on the growth of drug-naïve recipient cancer cells.</p><p><strong>Methods: </strong>EVs were isolated from cisplatin-treated and untreated SHH and group 3 medulloblastoma cells, as well as from the blood of mice with orthotopic medulloblastoma tumors. EVs were characterized using nanoparticle tracking analysis, cryo-TEM, and western blotting, and their impact on the growth of recipient medulloblastoma cells in 2D and 3D cultures was assessed. EV-miRNAs were analyzed using small RNA sequencing and qPCR, and the effects of candidate miRNA overexpression on medulloblastoma cell growth and apoptosis were evaluated.</p><p><strong>Results: </strong>We demonstrate that apoptotic SHH and group 3 medulloblastoma cells secrete increased numbers of EVs (size range 150-600 nm) both in vitro and in vivo. EVs isolated from cisplatin-treated SHH and group 3 medulloblastoma cells were internalized by recipient medulloblastoma cells and exhibited distinct effects on their growth. EVs from cisplatin-treated SHH medulloblastoma cells reduced clonogenic growth in recipient drug-naïve medulloblastoma cells, whereas EVs from cisplatin-treated group 3 medulloblastoma cells enhanced the clonogenic and sphere-forming capacity of recipient cells. These contrasting effects were associated with significant alterations in EV-miRNA expression profiles between untreated and cisplatin-treated SHH and group 3 medulloblastoma cells. Notably, miR-449a was found to be upregulated in EVs from cisplatin-treated SHH medulloblastoma cells, and its overexpression in medulloblastoma cells led to potent inhibition of growth.</p><p><strong>Conclusions: </strong>Our findings demonstrate, for the first time, that cisplatin-treated medulloblastoma cells from distinct molecular subgroups secrete EVs with altered miRNA expression profiles that either inhibit or promote the growth of recipient cancer cells. This underscores the potential of targeting EV-mediated communication as a novel therapeutic strategy in medulloblastoma.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"273"},"PeriodicalIF":8.2,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroangiogenesis potential of mesenchymal stem cell extracellular vesicles in ischemic stroke conditions.","authors":"Behnaz Mirzaahmadi, Shahin Ahmadian, Parinaz Haddadi, Parinaz Nezhad-Mokhtari, Fereshteh Vaziri Nezamdoust, Banafsheh Yalameha, Sara Aghakhani Chegeni, Somayyeh Rashidi, Akbar Mousakhani, Emel Sokullu, Hajar Shafaei, Reza Rahbarghazi, Mohammad Karimipour","doi":"10.1186/s12964-025-02286-w","DOIUrl":"10.1186/s12964-025-02286-w","url":null,"abstract":"<p><p>Ischemic stroke (IS) is a life-threatening condition in humans with high morbidity and mortality rates in developing and industrialized countries. The occlusion of blood-supporting vessels by thrombus or emboli can contribute to massive brain cell damage, neurological deficits, and long-term disability, and in more severe conditions, results in sudden death. Current therapeutic strategies, along with rehabilitation, in part, but not completely, can restore the integrity and function of the brain. These features necessitate the advent of novel therapeutic protocols for yielding better regenerative outcomes in IS patients. In past decades, the discovery of stem cells and byproducts has led to promising results in in vitro settings and pre-clinical studies. Extracellular vesicles (EVs) are nano-sized particles released from various cell types, for instance, mesenchymal stem cells (MSCs), with certain signaling biomolecules, growth factors, and cytokines involved in cell-to-cell communication. A great plethora of studies have pointed to the fact that EVs with specific cargo can distribute easily in different parts of the body, making them appropriate therapeutics under different pathological conditions. The current review articles aimed to highlight the neuroangiogenesis properties of MSC EVs in IS conditions. How and by which mechanisms MSC EVs can orchestrate the process of nervous system regeneration is at the center of debate. We think that the current article can help us better understand MSC EVs' function in the restoration of brain function under IS conditions in terms of neurogenesis and angiogenesis.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"272"},"PeriodicalIF":8.2,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}