Journal: Frontiers in Oncology

Article Title: Glia-derived VCAM1 promotes glioma progression

doi: 10.3389/fonc.2026.1802953

Figure Lengend Snippet: VCAM1 is expressed in glioma stem cells of eGFP+ 73C and eGFP+ GL261-luc tumor models in vivo. (A) Schematic timeline illustrating glioma cell implantation and acute cell staining. Gliomas were induced by intracranial implantation of 5,000–6,000 eGFP + 73C or eGFP + GL261-luc tumor cells in C57BL/6J mice. Acute cell staining was performed on day 12 post-implantation for eGFP + 73C and on day 20 for eGFP + GL261-luc. (B) Co-staining of VCAM1 with other glioma stem cell markers (SOX2, CD133, Nestin) and Ki-67 in acutely isolated eGFP + 73C glioma at 12 days post-implantation. Scale bar, 10 μm. (C) Co-staining of VCAM1 with other glioma stem cell markers (SOX2, CD133, Nestin) and Ki-67 in acutely isolated eGFP + GL261-luc glioma at 20 days post-implantation. Scale bar, 10 μm. (D) Quantitative analysis of the percentage of VCAM1-expressing cells in different glioma stem cell type populations in eGFP + 73C glioma. Data represent mean ± SEM (n = 6 biological replicates). Six randomly selected 500 × 500 μm regions were analyzed per sample. (E) Quantitative analysis of the percentage of VCAM1-expressing cells in different glioma stem cell type populations in eGFP + GL261-luc glioma. Data represent mean ± SEM, n = 6 repeats. Six 500 μm×500 μm regions were randomly selected.

Article Snippet: C57BL/6J (stock#000664), Ai14 line (stock #007914), GLAST-CreER line(stock#012586), VCAM1 fl/fl (stock#007665) were purchased from Jackson Laboratory.

Techniques: In Vivo, Staining, Isolation, Expressing

Journal: Frontiers in Oncology

Article Title: Glia-derived VCAM1 promotes glioma progression

doi: 10.3389/fonc.2026.1802953

Figure Lengend Snippet: VCAM1 is expressed in glioma stem cell-like cells of gDAM-induced primary glioma in vivo . (A) Schematic timeline for the application of the gDAM method in C57BL/6J mice, involving the injection of a plasmid combination and proline mixture for gliomagenesis. (B) Labeling of tdTomato-expressing astrocytes in the brain of Ai14 mice using a Cre-expressing plasmid delivered via the gDAM method. Scale bar, 100 μm. (C) An astrocyte expressing tdTomato with characteristic endfoot structures. Scale bar, 20 μm. (D) gDAM-induced primary glioma observed at five months, showing immunostaining for Ki67 (green), VCAM1 (purple), and mCherry + tumor cells (red). Scale bar, 2 mm. (E) SOX2-expressing mCherry + tumor cells in a five-month-old primary glioma, indicated by yellow arrows. Scale bar, 20 μm. (F) Expression patterns of VCAM1, SOX2 and tumor cells in GC and TSM. GC, glioma core; TSM, tumor substantial margins. Scale bar, 20 μm. (G) The proportion of SOX2 + mCherry + cells relative to the total mCherry + cells in the GC and the TSM. * p = 0.0313. Data are presented as mean ± SEM (n = 6 randomly selected fields derived from 3 mice per group). Statistical significance was determined by unpaired two-tailed Student’s t-test. (H) Relative fluorescence intensity of VCAM1 in the GC and TSM, based on randomly selected 200 μm × 200 μm regions. n.s. p = 0.1563. Data are presented as mean ± SEM (n = 6 randomly selected fields derived from 3 mice per group). Statistical significance was determined by unpaired two-tailed Student’s t-test.

Article Snippet: C57BL/6J (stock#000664), Ai14 line (stock #007914), GLAST-CreER line(stock#012586), VCAM1 fl/fl (stock#007665) were purchased from Jackson Laboratory.

Techniques: In Vivo, Injection, Plasmid Preparation, Labeling, Expressing, Immunostaining, Derivative Assay, Two Tailed Test, Fluorescence

Journal: Frontiers in Oncology

Article Title: Glia-derived VCAM1 promotes glioma progression

doi: 10.3389/fonc.2026.1802953

Figure Lengend Snippet: VCAM1 is expressed in a subset of GLAST+ astrocytes in glioma-bearing mice. (A) Experimental timeline for glioma cell implantation in GLAST-CreER::Ai14 mice. Mice received daily intraperitoneal injections of tamoxifen (TAM) for one week, followed by a one-week resting period. On day 1, 5,000-6,000 eGFP + 73C or GL261-luc glioma cells were implanted beneath the hippocampus. Tumor-bearing mice were harvested on day 10 (eGFP + 73C) or day 20 (GL261-luc). (B) Immunofluorescence staining of VCAM1 in eGFP + 73C gliomas at day 10 post-implantation of GLAST-CreER::Ai14 mice. Scale bars: (B) 1 mm; (a), 500 μm; (a’, b’), 100μm. (C) Immunofluorescence staining of VCAM1 in GL261-luc gliomas at day 20 post-implantation of GLAST-CreER::Ai14 mice. Scale bars: (C) 1 mm; (a), 500 μm; (a’), 100 μm.

Article Snippet: C57BL/6J (stock#000664), Ai14 line (stock #007914), GLAST-CreER line(stock#012586), VCAM1 fl/fl (stock#007665) were purchased from Jackson Laboratory.

Techniques: Immunofluorescence, Staining

Journal: Frontiers in Oncology

Article Title: Glia-derived VCAM1 promotes glioma progression

doi: 10.3389/fonc.2026.1802953

Figure Lengend Snippet: Knockout of VCAM1 in GLAST+ cells prolongs mouse survival. (A) Experimental timeline for glioma cell implantation in GLAST-CreER::VCAM1 fl/fl and control mice. Mice received daily intraperitoneal injections of tamoxifen (TAM) for one week, followed by a one-week waiting period. On day 1, 5,000-6,000 tumor cells were injected into the cortex or below the hippocampus. Live imaging analysis was conducted at the predetermined points. (B) Kaplan-Meier survival curves of mice implanted with eGFP+ 73C tumor cells below the hippocampus. Control group (n = 6), GLAST-CreER::VCAM1fl/fl group (n = 6). p-value calculated using the log-rank Mantel-Cox test. Control vs GLAST-CreER::VCAM1fl/fl, “ns” indicates no statistical significance ( p > 0.05). Here, p = 0.1209. (C) Kaplan-Meier survival curves of mice implanted with eGFP+ 73C tumor cells in the cortex. Control group (n = 6), GLAST-CreER::VCAM1fl/fl group (n = 6). p-value calculated using the log-rank Mantel-Cox test. Control vs GLAST-CreER::VCAM1fl/fl, ** p = 0.0053. (D) Live imaging analysis of GL261-luc-bearing mice in hippocampus GLAST-CreER::VCAM1 fl/fl and control groups at days 9, 28 and 50. (E) Kaplan-Meier survival curves of mice implanted with GL261-luc tumor cells below the hippocampus. Control group (n = 7), GLAST-CreER::VCAM1 fl/fl group (n = 6). p -value calculated using the log-rank Mantel-Cox test. Control vs. GLAST-CreER::VCAM1 fl/fl , * p = 0.0223. (F) Longitudinal quantification of tumor burden by bioluminescence imaging (Total Flux) in the Hippocampus GL261-luc models. Data are presented as mean ± SEM. Statistical significance was evaluated using Two-way repeated measures ANOVA. The asterisks indicate a significant interaction effect between time and genotype, ** p = 0.0082. Data are presented as mean ± SEM (n = 6–7 mice per group). Statistical significance was evaluated using two-way repeated measures ANOVA. (G) Live imaging analysis of GL261-luc-bearing mice in cortex from the GLAST-CreER::VCAM1 fl/fl and control groups at days 20, 40, 60. (H) Kaplan-Meier survival curves of mice implanted with GL261-luc tumor cells in the cortex. Control group (n = 7), GLAST-CreER::VCAM1 fl/fl group (n = 6). p -value calculated using the log-rank Mantel-Cox test. Control vs. GLAST-CreER::VCAM1 fl/fl , * p = 0.0465. (I) Longitudinal quantification of tumor burden by bioluminescence imaging (Total Flux) in the Cortex GL261-luc models. Data are presented as mean ± SEM. Statistical significance was evaluated using Two-way repeated measures ANOVA. The asterisks indicate a significant interaction effect between time and genotype, * p = 0.0106. Data are presented as mean ± SEM (n = 6–7 mice per group). Statistical significance was evaluated using two-way repeated measures ANOVA.

Article Snippet: C57BL/6J (stock#000664), Ai14 line (stock #007914), GLAST-CreER line(stock#012586), VCAM1 fl/fl (stock#007665) were purchased from Jackson Laboratory.

Techniques: Knock-Out, Control, Injection, Imaging

Journal: Frontiers in Oncology

Article Title: Glia-derived VCAM1 promotes glioma progression

doi: 10.3389/fonc.2026.1802953

Figure Lengend Snippet: The RNA-seq reveals the changes of TME following astrocytic VCAM1 deletion. (A) The protocol of RNA-seq on tumor associated VCAM1-deficient GLAST positive astrocytes. n = 6 biological replicates per group (derived from 3 mice per group, 2 independent samples per mouse) were analyzed. (B) Differentially expressed genes in astrocytic VCAM1-deficient TME. (C, F) The KEGG and GO enrichment analysis of our inhouse dataset. (D, E, G, H) The GSEA analysis of differentially expressed genes identified several functional pathways, antigen processing and presentation, cell adhesion, oxidative phosphorylation, and cholesterol efflux.

Article Snippet: C57BL/6J (stock#000664), Ai14 line (stock #007914), GLAST-CreER line(stock#012586), VCAM1 fl/fl (stock#007665) were purchased from Jackson Laboratory.

Techniques: RNA Sequencing, Derivative Assay, Functional Assay, Phospho-proteomics

Journal: Frontiers in Oncology

Article Title: Glia-derived VCAM1 promotes glioma progression

doi: 10.3389/fonc.2026.1802953

Figure Lengend Snippet: Clinical relevance of VCAM1 expression in human gliomas based on public database analysis. (A) Kaplan-Meier survival curve of patients with lower grade glioma and glioblastoma (GBMLGG) with different expression levels of VCAM1 in TCGA. The p-value was calculated using log-rank test (Mantel-Cox test). VCAM1>=9.605 (n=351) vs VCAM1<9.605 (n=343) *** p = 0.000001255. (B) Kaplan-Meier survival curve of patients with lower grade glioma (LGG) with different expression levels of VCAM1 in TCGA. The p-value was calculated using Mantel-Cox test. VCAM1>=9.243 (n=265) vs VCAM1<9.243 (n=263) ** p = 0.001199. (C) Kaplan-Meier survival curve of patients with glioblastoma (GBM) with different expression levels of VCAM1 in TCGA. The p-value was calculated using Mantel-Cox test. VCAM1>=10.25 (n=86) vs VCAM1<10.25 (n=80) ns p = 0.8022. (D) A 32-year-old female with moderate staining intensity of VCAM1 protein expression in LGG. Images were obtained from the Human Protein Atlas (HPA) database.

Article Snippet: C57BL/6J (stock#000664), Ai14 line (stock #007914), GLAST-CreER line(stock#012586), VCAM1 fl/fl (stock#007665) were purchased from Jackson Laboratory.

Techniques: Expressing, Staining

Journal: Frontiers in Oncology

Article Title: Glia-derived VCAM1 promotes glioma progression

doi: 10.3389/fonc.2026.1802953

Figure Lengend Snippet: VCAM1 is expressed in glioma stem cells of eGFP+ 73C and eGFP+ GL261-luc tumor models in vivo. (A) Schematic timeline illustrating glioma cell implantation and acute cell staining. Gliomas were induced by intracranial implantation of 5,000–6,000 eGFP + 73C or eGFP + GL261-luc tumor cells in C57BL/6J mice. Acute cell staining was performed on day 12 post-implantation for eGFP + 73C and on day 20 for eGFP + GL261-luc. (B) Co-staining of VCAM1 with other glioma stem cell markers (SOX2, CD133, Nestin) and Ki-67 in acutely isolated eGFP + 73C glioma at 12 days post-implantation. Scale bar, 10 μm. (C) Co-staining of VCAM1 with other glioma stem cell markers (SOX2, CD133, Nestin) and Ki-67 in acutely isolated eGFP + GL261-luc glioma at 20 days post-implantation. Scale bar, 10 μm. (D) Quantitative analysis of the percentage of VCAM1-expressing cells in different glioma stem cell type populations in eGFP + 73C glioma. Data represent mean ± SEM (n = 6 biological replicates). Six randomly selected 500 × 500 μm regions were analyzed per sample. (E) Quantitative analysis of the percentage of VCAM1-expressing cells in different glioma stem cell type populations in eGFP + GL261-luc glioma. Data represent mean ± SEM, n = 6 repeats. Six 500 μm×500 μm regions were randomly selected.

Article Snippet: Furthermore, evaluation of VCAM1 protein expression via The Human Protein Atlas (HPA) revealed variable staining intensities among glioma patients ( ).

Techniques: In Vivo, Staining, Isolation, Expressing

Journal: Frontiers in Oncology

Article Title: Glia-derived VCAM1 promotes glioma progression

doi: 10.3389/fonc.2026.1802953

Figure Lengend Snippet: VCAM1 is expressed in glioma stem cell-like cells of gDAM-induced primary glioma in vivo . (A) Schematic timeline for the application of the gDAM method in C57BL/6J mice, involving the injection of a plasmid combination and proline mixture for gliomagenesis. (B) Labeling of tdTomato-expressing astrocytes in the brain of Ai14 mice using a Cre-expressing plasmid delivered via the gDAM method. Scale bar, 100 μm. (C) An astrocyte expressing tdTomato with characteristic endfoot structures. Scale bar, 20 μm. (D) gDAM-induced primary glioma observed at five months, showing immunostaining for Ki67 (green), VCAM1 (purple), and mCherry + tumor cells (red). Scale bar, 2 mm. (E) SOX2-expressing mCherry + tumor cells in a five-month-old primary glioma, indicated by yellow arrows. Scale bar, 20 μm. (F) Expression patterns of VCAM1, SOX2 and tumor cells in GC and TSM. GC, glioma core; TSM, tumor substantial margins. Scale bar, 20 μm. (G) The proportion of SOX2 + mCherry + cells relative to the total mCherry + cells in the GC and the TSM. * p = 0.0313. Data are presented as mean ± SEM (n = 6 randomly selected fields derived from 3 mice per group). Statistical significance was determined by unpaired two-tailed Student’s t-test. (H) Relative fluorescence intensity of VCAM1 in the GC and TSM, based on randomly selected 200 μm × 200 μm regions. n.s. p = 0.1563. Data are presented as mean ± SEM (n = 6 randomly selected fields derived from 3 mice per group). Statistical significance was determined by unpaired two-tailed Student’s t-test.

Article Snippet: Furthermore, evaluation of VCAM1 protein expression via The Human Protein Atlas (HPA) revealed variable staining intensities among glioma patients ( ).

Techniques: In Vivo, Injection, Plasmid Preparation, Labeling, Expressing, Immunostaining, Derivative Assay, Two Tailed Test, Fluorescence

Journal: Frontiers in Oncology

Article Title: Glia-derived VCAM1 promotes glioma progression

doi: 10.3389/fonc.2026.1802953

Figure Lengend Snippet: VCAM1 is expressed in a subset of GLAST+ astrocytes in glioma-bearing mice. (A) Experimental timeline for glioma cell implantation in GLAST-CreER::Ai14 mice. Mice received daily intraperitoneal injections of tamoxifen (TAM) for one week, followed by a one-week resting period. On day 1, 5,000-6,000 eGFP + 73C or GL261-luc glioma cells were implanted beneath the hippocampus. Tumor-bearing mice were harvested on day 10 (eGFP + 73C) or day 20 (GL261-luc). (B) Immunofluorescence staining of VCAM1 in eGFP + 73C gliomas at day 10 post-implantation of GLAST-CreER::Ai14 mice. Scale bars: (B) 1 mm; (a), 500 μm; (a’, b’), 100μm. (C) Immunofluorescence staining of VCAM1 in GL261-luc gliomas at day 20 post-implantation of GLAST-CreER::Ai14 mice. Scale bars: (C) 1 mm; (a), 500 μm; (a’), 100 μm.

Article Snippet: Furthermore, evaluation of VCAM1 protein expression via The Human Protein Atlas (HPA) revealed variable staining intensities among glioma patients ( ).

Techniques: Immunofluorescence, Staining

Journal: Frontiers in Oncology

Article Title: Glia-derived VCAM1 promotes glioma progression

doi: 10.3389/fonc.2026.1802953

Figure Lengend Snippet: Knockout of VCAM1 in GLAST+ cells prolongs mouse survival. (A) Experimental timeline for glioma cell implantation in GLAST-CreER::VCAM1 fl/fl and control mice. Mice received daily intraperitoneal injections of tamoxifen (TAM) for one week, followed by a one-week waiting period. On day 1, 5,000-6,000 tumor cells were injected into the cortex or below the hippocampus. Live imaging analysis was conducted at the predetermined points. (B) Kaplan-Meier survival curves of mice implanted with eGFP+ 73C tumor cells below the hippocampus. Control group (n = 6), GLAST-CreER::VCAM1fl/fl group (n = 6). p-value calculated using the log-rank Mantel-Cox test. Control vs GLAST-CreER::VCAM1fl/fl, “ns” indicates no statistical significance ( p > 0.05). Here, p = 0.1209. (C) Kaplan-Meier survival curves of mice implanted with eGFP+ 73C tumor cells in the cortex. Control group (n = 6), GLAST-CreER::VCAM1fl/fl group (n = 6). p-value calculated using the log-rank Mantel-Cox test. Control vs GLAST-CreER::VCAM1fl/fl, ** p = 0.0053. (D) Live imaging analysis of GL261-luc-bearing mice in hippocampus GLAST-CreER::VCAM1 fl/fl and control groups at days 9, 28 and 50. (E) Kaplan-Meier survival curves of mice implanted with GL261-luc tumor cells below the hippocampus. Control group (n = 7), GLAST-CreER::VCAM1 fl/fl group (n = 6). p -value calculated using the log-rank Mantel-Cox test. Control vs. GLAST-CreER::VCAM1 fl/fl , * p = 0.0223. (F) Longitudinal quantification of tumor burden by bioluminescence imaging (Total Flux) in the Hippocampus GL261-luc models. Data are presented as mean ± SEM. Statistical significance was evaluated using Two-way repeated measures ANOVA. The asterisks indicate a significant interaction effect between time and genotype, ** p = 0.0082. Data are presented as mean ± SEM (n = 6–7 mice per group). Statistical significance was evaluated using two-way repeated measures ANOVA. (G) Live imaging analysis of GL261-luc-bearing mice in cortex from the GLAST-CreER::VCAM1 fl/fl and control groups at days 20, 40, 60. (H) Kaplan-Meier survival curves of mice implanted with GL261-luc tumor cells in the cortex. Control group (n = 7), GLAST-CreER::VCAM1 fl/fl group (n = 6). p -value calculated using the log-rank Mantel-Cox test. Control vs. GLAST-CreER::VCAM1 fl/fl , * p = 0.0465. (I) Longitudinal quantification of tumor burden by bioluminescence imaging (Total Flux) in the Cortex GL261-luc models. Data are presented as mean ± SEM. Statistical significance was evaluated using Two-way repeated measures ANOVA. The asterisks indicate a significant interaction effect between time and genotype, * p = 0.0106. Data are presented as mean ± SEM (n = 6–7 mice per group). Statistical significance was evaluated using two-way repeated measures ANOVA.

Article Snippet: Furthermore, evaluation of VCAM1 protein expression via The Human Protein Atlas (HPA) revealed variable staining intensities among glioma patients ( ).

Techniques: Knock-Out, Control, Injection, Imaging

Journal: Frontiers in Oncology

Article Title: Glia-derived VCAM1 promotes glioma progression

doi: 10.3389/fonc.2026.1802953

Figure Lengend Snippet: The RNA-seq reveals the changes of TME following astrocytic VCAM1 deletion. (A) The protocol of RNA-seq on tumor associated VCAM1-deficient GLAST positive astrocytes. n = 6 biological replicates per group (derived from 3 mice per group, 2 independent samples per mouse) were analyzed. (B) Differentially expressed genes in astrocytic VCAM1-deficient TME. (C, F) The KEGG and GO enrichment analysis of our inhouse dataset. (D, E, G, H) The GSEA analysis of differentially expressed genes identified several functional pathways, antigen processing and presentation, cell adhesion, oxidative phosphorylation, and cholesterol efflux.

Article Snippet: Furthermore, evaluation of VCAM1 protein expression via The Human Protein Atlas (HPA) revealed variable staining intensities among glioma patients ( ).

Techniques: RNA Sequencing, Derivative Assay, Functional Assay, Phospho-proteomics

Journal: Frontiers in Oncology

Article Title: Glia-derived VCAM1 promotes glioma progression

doi: 10.3389/fonc.2026.1802953

Figure Lengend Snippet: Clinical relevance of VCAM1 expression in human gliomas based on public database analysis. (A) Kaplan-Meier survival curve of patients with lower grade glioma and glioblastoma (GBMLGG) with different expression levels of VCAM1 in TCGA. The p-value was calculated using log-rank test (Mantel-Cox test). VCAM1>=9.605 (n=351) vs VCAM1<9.605 (n=343) *** p = 0.000001255. (B) Kaplan-Meier survival curve of patients with lower grade glioma (LGG) with different expression levels of VCAM1 in TCGA. The p-value was calculated using Mantel-Cox test. VCAM1>=9.243 (n=265) vs VCAM1<9.243 (n=263) ** p = 0.001199. (C) Kaplan-Meier survival curve of patients with glioblastoma (GBM) with different expression levels of VCAM1 in TCGA. The p-value was calculated using Mantel-Cox test. VCAM1>=10.25 (n=86) vs VCAM1<10.25 (n=80) ns p = 0.8022. (D) A 32-year-old female with moderate staining intensity of VCAM1 protein expression in LGG. Images were obtained from the Human Protein Atlas (HPA) database.

Article Snippet: Furthermore, evaluation of VCAM1 protein expression via The Human Protein Atlas (HPA) revealed variable staining intensities among glioma patients ( ).

Techniques: Expressing, Staining

Journal: Scientific Reports

Article Title: Sex-related differences in cardiovascular inflammation and metabolomics in a humanized transgenic mouse model of celiac disease

doi: 10.1038/s41598-026-45481-6

Figure Lengend Snippet: Cardiovascular tissues and cholesterol levels of female NOD-DQ8 mice show no inflammatory response to active CeD. ( A – C ) Transcript levels of biomarkers for inflammation and oxidative stress were analysed in tissue of the left ventricle by qPCR. Vascular cell adhesion molecule 1 (VCAM1), tumor necrosis factor alpha (TNFα), and inducible NO synthase (iNos/Nos2) were significantly elevated on mRNA level in males. Heart tissue of NOD-DQ8 females showed no differences in the tested groups. ( D – F ) The same biomarkers were tested in aortic tissue, too. Glutenexposed males showed a severe increase of inflammatory markers. Again, females did not develop such a phenotype. ( G – I ) By colorimetric enzymatic testing, the same pattern was observed regarding levels of serum cholesterol. Gluten-fed males displayed increased cholesterol levels while females showed no diet-induced alterations. ( A – I ) Bar graphs show the arithmetic mean and SD. One-way ANOVA, n = 6–9; * is p < 0.05; ** is p < 0.01; *** p < 0.001; **** is p < 0.0001.

Article Snippet: The applied TaqMan primer are Vcam1 (Mm00449197_m1), Tnfα (Mm00443259_g1), iNOS /Nos2 (Mm00440485_m1), and Tbp (Mm00446973_m1).

Techniques: