Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2025, Volume and Issue: unknown, P. 189341 - 189341
Published: May 1, 2025
Language: Английский
Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(1), P. 75 - 75
Published: Jan. 10, 2025
Recent developments in single-cell multi-omics technologies have provided the ability to identify diverse cell types and decipher key components of tumor microenvironment (TME), leading important advancements toward a much deeper understanding how heterogeneity contributes cancer progression therapeutic resistance. These are able integrate data from molecular genomic, transcriptomic, proteomics, metabolomics studies cells at resolution scale that give rise full cellular complexity TME. Understanding complex sometimes reciprocal relationships among cells, CAFs, immune ECs has led novel insights into their immense functions, which can consequences on behavior. In-depth uncovered evasion mechanisms, including exhaustion T metabolic reprogramming response hypoxia cells. Single-cell also revealed resistance such as stromal cell-secreted factors physical barriers extracellular matrix. Future examining specific pathways targeting approaches reduce TME will likely lead better outcomes with immunotherapies, drug delivery, etc., for treatments. incorporate data, spatial micro-environments, translation personalized therapies. This review emphasizes provide TME, revealing reprogramming, influences. aim guide development targeted therapies, highlighting role diversity shaping behavior treatment outcomes.
Language: Английский
Citations
8
Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15
Published: Jan. 21, 2025
Emerging evidence indicates a correlation between inflammation and the development progression of cancer. Among various inflammatory signals, interleukin-17 (IL-17) family cytokines serve as critical link IL-17 is highly versatile pro-inflammatory cytokine that plays pivotal role in host defense, tissue repair, pathogenesis diseases, cancer progression. During early stages tumorigenesis, signaling directly promotes proliferation tumor cells. Conversely, has been shown to exhibit antitumor immunity several models grafted subcutaneous tumors. Additionally, dynamic changes microbiome can influence secretion IL-17, thereby affecting development. The specific contingent upon its functional classification, spatiotemporal characteristics, stage In this review, we introduce fundamental biology expression profile receptors cancer, while also reviewing discussing recent advancements regarding pleiotropic effects mechanisms inflammation-related cancers. Furthermore, supplement our discussion with insights into by which impacts through interactions microbiota, explore implications therapy. This comprehensive analysis aims enhance understanding potential treatment.
Language: Английский
Citations
4
Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(4)
Published: April 1, 2024
Abstract Background IL‐17A and TNF synergistically promote inflammation tumorigenesis. Their interplay impact on ovarian carcinoma (OC) progression are, however, poorly understood. We addressed this question focusing mesothelial cells, whose interaction with tumor cells is known to play a pivotal role in transcoelomic metastasis formation. Methods Flow‐cytometry immunohistochemistry experiments were employed identify cellular sources of TNF. Changes transcriptomes secretomes determined by bulk single cell RNA sequencing as well affinity proteomics. Functional consequences investigated microscopic analyses adhesion assays. Potential clinical implications assessed survival analyses. Results identified Th17 the main population IL‐17A‐ producers ascites detected their accumulation early omental metastases. Both its receptor subunit IL‐17RC associated short OC patients, pointing progression. induced reprogramming towards pro‐inflammatory mesenchymal phenotype, concomitantly loss tight junctions an impairment monolayer integrity, thereby promoting cancer adhesion. Th17‐promoting cytokines IL‐6 IL‐1β Th17‐attracting chemokine CCL20 indicating reciprocal crosstalk that potentiates tumor‐promoting OC. Conclusions Our findings reveal novel function for microenvironment, which entails IL‐17A/TNF‐mediated induction mesothelial‐mesenchymal transition, disruption layer integrity consequently promotion These effects are potentiated positive feedback loop between cells. Together observed associations micrometastases, our observations point potential metastases formation thus new therapeutic options.
Language: Английский
Citations
10
Nature Immunology, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 24, 2025
Language: Английский
Citations
0
Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)
Published: March 13, 2025
Abstract Background High expression of basal cell adhesion molecule (BCAM) is a hallmark ovarian cancer (OC) progression. BCAM facilitates transcoelomic dissemination by promoting mesothelial clearance at peritoneal attachment sites tumor spheroids. We investigated how mediates this effect and potentially drives other pro-metastatic functions. Methods The impact on the secretome phenotype was analyzed affinity proteomics, bulk single-cell RNA sequencing, life-cell multiphoton microscopy, biochemical functional in vitro assays as well murine model. manipulation involved ectopic overexpression, inducible treatment with soluble BCAM. Results All forms enhanced secretion cytokines that motility, mesenchymal differentiation angiogenesis, including AREG, CXCL family members, FGF2, TGFB2, VEGF. Notably, their levels OC ascites were correlated expression, recombinant BCAM-induced triggered mesothelial-mesenchymal transition (MMT). Mesothelial cells undergoing MMT exhibited motility away from attaching spheroids, leading to spheroid sites. BCAM-mediated MMT-associated transcriptional changes also observed subpopulations omental patients, associated poor survival. Consistent data, induced endothelial tube formation markedly promoted angiogenesis mouse Conclusion have identified previously unknown functions impacting distinct stages metastasis. While BCAM’s may facilitate initiation micrometastases, neo-angiogenesis essential for growth. Taken together clinical adverse association, our findings underscore potential therapeutic target.
Language: Английский
Citations
0
Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(7)
Published: April 1, 2025
ABSTRACT Circadian disruptions and neuroinflammation impact nearly all people with Alzheimer's disease (AD), but their relationships each other the of interaction on AD remain to be addressed. Here, we found that amyloid (A)‐β treatment downregulated brain muscle aryl hydrocarbon receptor nuclear translocator‐like (BMAL) 1 through hypermethylation its promoter region in HT22 cells inhibition DNA methylation ameliorated circadian rhythm disorders restored BMAL1 protein expression by reversing APPswe/PSEN1dE9 (APP/PS1) mice. Critically, increased levels interleukin (IL)‐17A contributed downregulation region, thus leading APP/PS1 Moreover, revealed mitogen‐activated kinase (MAPK) pathway was responsible for IL‐17A‐induced methyltransferase (DNMT) upregulation. Taken together, elucidate a new mechanism connecting IL‐17A altered Bmal1 , which results disturbances an mouse model.
Language: Английский
Citations
0
International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4041 - 4041
Published: April 24, 2025
Ovarian cancer is one of the most deadly gynecological cancers, with over 300 thousand new cases per year, which are diagnosed in advanced stages. The limited availability effective biomarkers and lack characteristic symptoms make early diagnosis difficult, resulting a five-year survival rate 30–40%. Mutations BRCA1 BRCA2 genes abnormalities signaling pathways such as PI3K/AKT TP53 play key role progression ovarian cancer. immune system, can act against tumors, often supports tumor development microenvironment through immunoevasion, influenced by cytokines IL-6, IL-10, TGF-β. Epithelial-to-mesenchymal transition (EMT) allows cells to acquire mesenchymal characteristics, increasing their invasiveness metastatic capacity. Immunological factors, including pro-inflammatory signals from regulate EMT process. This review aims present progression, its interactions potential therapeutic targets. Modulation response inhibition may constitute basis for personalized therapies, opens possibilities improving prognosis efficacy treatment patients
Language: Английский
Citations
0
Trends in Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown
Published: April 1, 2025
Language: Английский
Citations
0
Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16
Published: April 30, 2025
Chronic inflammation is a key contributor to carcinogenesis, progression, and chemoresistance in ovarian cancer, making inflammatory pathways logical therapeutic target for the treatment of this disease. Sulindac, commonly used non-steroidal anti-inflammatory drug, has demonstrated anti-proliferative anti-invasive effects on several preclinical models cancer. In study, we investigated antitumorigenic sulindac human cancer cell lines transgenic mouse model (KpB). MTT colony formation assays were evaluate proliferation. Cell cycle was detected by Cellometer. ELISA conducted changes cellular stress, apoptosis adhesion, while invasion determined wound healing assay. Protein expression examined through Western blotting immunohistochemistry. Our results that significantly inhibited proliferation, induced stress apoptosis, caused G1 phase arrest, reduced invasion, suppressed Cox-2 NF-κB MES OVCAR5 lines. Inhibition N-acetylcysteine partially reversed sulindac. The combination paclitaxel produced synergistic inhibiting growth both sensitive resistant cells. Treatment with 4 weeks effectively tumor growth, improved serum levels cytokines chemokines, tumors KpB mice compared untreated mice. These findings provide support development clinical trials repurposing OC, possibly paclitaxel.
Language: Английский
Citations
0
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2025, Volume and Issue: unknown, P. 189341 - 189341
Published: May 1, 2025
Language: Английский
Citations
0