Pro-Inflammatory Cytokines Transactivate Glycosylated Cytokine Receptors on Cancer Cells to Induce Epithelial–Mesenchymal Transition to the Metastatic Phenotype

Cancers, Journal Year: 2025, Volume and Issue: 17(7), P. 1234 - 1234

Published: April 5, 2025

Background/Objectives: The significance of cytokine signaling on cancer progression and metastasis has raised interest in research over the last few decades. Here, we analyzed effects three cytokines that previously reported are significantly upregulated rapidly after surgical removal primary breast, colorectal, prostate cancer. We also investigated regulation their cognate receptors. Methods: All experiments were conducted using PANC-1, SW620, MCF-7 cell lines, treated with different (TGF-β1, HGF, IL-6). effect these expression epithelial-mesenchymal transition (EMT) surface markers neuraminidase-1 activity was measured via fluorescent microscopy image analysis software. Results: findings show increase mesenchymal while reducing epithelial markers, corresponding to EMT process. A strong link between receptor Neu-1-MMP-9-GPCR crosstalk identified, suggesting binding leads increased Neu-1 subsequent pathway activation. Oseltamivir phosphate (OP) prevented sialic acid hydrolysis by (Neu-1), leading downregulation cascades. Conclusions: In concert previous work revealing role regulating other glycosylated receptors implicated proliferation EMT, targeting may provide effective treatment against a variety malignancies. Most significantly, patients specific inhibitors soon surgery improve our ability cure early-stage inhibiting process disrupting any residual population metastasize.

Language: Английский

Single‐Cell Insights Into Cellular Response in Abdominal Aortic Occlusion‐Induced Hippocampal Injury

CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(1)

Published: Jan. 1, 2025

ABSTRACT Objective Ischemia–reperfusion of the abdominal aorta often results in damage to distant organs, such as heart and brain. This cellular heterogeneity within affected tissues complicates roles specific cell subsets occlusion model (AAO) injury. However, type–specific molecular pathology hippocampus after ischemia is poorly understood. Aims In this study, we adopted a mouse AAO investigate single‐cell transcriptome hippocampi mice. Methods Male C57BL/6 mice (8 weeks old) were used create an model, with animals divided into Sham I/R groups. The group was subjected 2 h followed by 24 reperfusion, which hippocampal collected for RNA sequencing histological analysis. Behavioral tests, including Rotarod, Y‐maze, new object recognition performed daily 28 days post‐surgery evaluate neurological function. A total 62,624 cells corresponding 7 types neuronal, glial, vascular lineages. We next analyzed cell‐specific gene alterations function these Genes. Results injury upregulated astrocyte oligodendrocyte precursor (OPC) proportions ( p ‐value < 0.05). Astrocytes showed unique expression related neurogenesis mRNA processing. Five distinct subtypes emerged post‐injury. OPCs exhibited enhanced synapse organization. Microglia activation elevated level epithelial oxidative phosphorylation protein–protein interaction (PPI) module indicate inflammatory response metabolic changes Conclusions Our scRNA‐seq analysis provides insights transcriptional at AAO‐induced study illustrates how region responds identifies potential therapeutic targets intervention, thereby paving way future research treatment strategies.

Language: Английский

Activity-Based Bioluminescent Logic-Gate Probe Reveals Crosstalk Between the Inflammatory Tumor Microenvironment and ALDH1A1 in Cancer Cells

JACS Au, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 28, 2024

Cancer cells with high expression of aldehyde dehydrogenase 1A1 (ALDH1A1) are more resistant to chemotherapy, contribute tumor progression, and associated poor clinical outcomes. ALDH1A1 plays a critical role in protecting from reactive aldehydes and, the case stem cells, regulates their differentiation through retinoic acid signaling pathway. Despite importance this enzyme, methods study high-expressing cancer vivo remain limited. In work, we developed AlDeLuc, first logic-gated bioluminescence probe designed selectively evaluate activity cells. The is sequentially activated by acidic intracellular compartments (i.e., endosomes) ALDH1A1, ensuring precise detection minimizing off-target non-ALDH1A1 Beyond demonstrating efficacy multiple cell lines murine model breast cancer, employed AlDeLuc investigate how population influenced inflammatory status context high-fat diet. These findings establish molecular link between obesity, inflammation, progression.

Language: Английский