Journal: Cancer research

Article Title: GDF15 Reprograms the Microenvironment to Drive Liver Metastasis of Uveal Melanoma

doi: 10.1158/0008-5472.CAN-25-0536

Figure Lengend Snippet: A: UMAP of 6 individual clinical UM “and healthy” scRNA-seq datasets. Data shows major cell types identified and then GDF15 expression in the UM cells (malignant cells) B: Violin plots showing expression of GDF15 in a scRNA-Seq analysis of human Class 1 and Class 2 UM. C: Western Blot showing the expression of BAP1, PRAME and GDF15 in a panel of UM cell lines. D: Silencing of BAP1 is associated with increased expression of GDF15 in Mel202 and 92.1 UM cells. BAP1 was silenced using siRNA and resulting lysates probed for expression of BAP1 and GDF15. E: ChIP-Seq analysis of Mel202 cells expressing BAP1 or silenced for BAP1 demonstrates an increase in H3K27ac at the GDF15 promoter following BAP1 knockdown. F: Analysis of GDF15 secretion by ELISA assay demonstrates that co-culture of UM cells with HSCs is associated with increased GDF15 expression, even in UM cell lines with high basal expression of GDF15. Cell lines derived from primary or metastatic specimens are indicated.

Article Snippet: The effectiveness of blocking GDF15 on tube formation was assessed using an anti-GDF15 blocking antibody (ponsegromab: 120ng/ml, #HY-P99241, MedChemExpress, NJ, USA).

Techniques: Expressing, Western Blot, ChIP-sequencing, Knockdown, Enzyme-linked Immunosorbent Assay, Co-Culture Assay, Derivative Assay

Journal: Cancer research

Article Title: GDF15 Reprograms the Microenvironment to Drive Liver Metastasis of Uveal Melanoma

doi: 10.1158/0008-5472.CAN-25-0536

Figure Lengend Snippet: A: RNA-seq analysis of HSCs (LX2) treated with GDF15 (1μg/ml, 24 hr) identifies increased expression of genes encoding multiple ECM proteins ( COL7A1 ), and molecules involved in angiogenesis ( VCAM1, ANGPLT4, PDGFB, FLT1 ). B: Pathway analysis identifies GDF15 to increase expression of genes involved in inflammatory signaling ( TNFA, IFNγ, IL6 ), angiogenesis (hypoxia, angiogenesis) and metabolism. C: Human primary HSCs (HHStec) were stimulated with either GDF15 (1μg/ml) or SPP1 (osteopontin, (1μg/ml)) for 24 hr and Western Blotting used to determine expression of IL-8 and phospho-STAT3. D: HSC (HHStec cells) were grown in monoculture, MP41 cells were grown in monoculture, HSC+MP41 cells were grown in co-culture, HSCs were treated with conditioned media (CM) from MP41 cells or GDF15 (1μg/ml) for 24 hr before probing for the expression of COL1A1 and PDGFRB by Western Blot. E: Immunofluorescence staining of COL1A1 in HSCs (HHStec) cells treated with basal media or conditioned media from MP41 or UMM061 cells. F: CellChat analysis of human UM samples identifies HSC-derived collagens as being a potential outgoing signal to multiple immune subtypes and UM cells.

Article Snippet: The effectiveness of blocking GDF15 on tube formation was assessed using an anti-GDF15 blocking antibody (ponsegromab: 120ng/ml, #HY-P99241, MedChemExpress, NJ, USA).

Techniques: Expressing, RNA Sequencing, Western Blot, Co-Culture Assay, Immunofluorescence, Staining, Derivative Assay

Journal: Cancer research

Article Title: GDF15 Reprograms the Microenvironment to Drive Liver Metastasis of Uveal Melanoma

doi: 10.1158/0008-5472.CAN-25-0536

Figure Lengend Snippet: A: CellChat analysis of scRNA-Seq from human UM identifies endothelial cells as being a major target of secreted GDF15. B: Exogenous GDF15 and IL8 increase vascular network formation. HUVEC cells were plated on Matrigel and treated with basal media, IL-8 or GDF15 (both 1μg/ml for 0–24 hr). C: Scoring of endothelial network formation data from B. D: Conditioned media (CM) from UM-HSC co-cultures increases vascular network formation. HUVECs were plated onto Matrigel and treated with basal media or CM from MP41, UMM061 and MM28 cells grown in co-culture with LX2 cells. E: Vascular network formation from D was quantified. F: GDF15-blocking antibodies reverse the pro-angiogenic effects of CM. HUVEC cells were treated with CM from MP41-LX2 co-cultures in the absence and presence of the GDF15 blocking antibody (Ponsegromab,120ng/ml) and vascular network formation imaged. G : Quantification of endothelial cell network formation from F.

Article Snippet: The effectiveness of blocking GDF15 on tube formation was assessed using an anti-GDF15 blocking antibody (ponsegromab: 120ng/ml, #HY-P99241, MedChemExpress, NJ, USA).

Techniques: Co-Culture Assay, Blocking Assay

Journal: Cancer research

Article Title: GDF15 Reprograms the Microenvironment to Drive Liver Metastasis of Uveal Melanoma

doi: 10.1158/0008-5472.CAN-25-0536

Figure Lengend Snippet: A: IVIS imaging of mice with either shCRTL or shGDF15#2 MP41 cells at days 49 and 77, respectively. B: Metastasis-free survival of mice following tail vein injection of either shCRTL or shGDF15#2 MP41 cells. C: H&E staining of livers following tail vein injection of shCRTL or GDF15 silenced (GDF15 shRNA#2) MP41 UM cells. Livers were collected after 7 weeks (shCRTL) or 11 weeks (shGDF15). Scale Bar = 6 mm. D: Quantification of liver metastases following tail vein injection of GDF15-expressing or silenced MP41 cells (GDF15 shRNA#1 and shRNA#2). E: IVIS imaging of mice with either shCRTL or shGDF15#2 OMM1 cells at days 56 and 70, respectively. F: Metastasis-free survival of mice following tail vein injection of either shCRTL or shGDF15#2 OMM1 cells. G: H&E staining of livers following tail vein injection of shCRTL or GDF15 silenced (GDF15 shRNA#2) OMM1 UM cells. Livers were collected after 7 weeks (shCRTL) or 11 weeks (shGDF15). Scale Bar = 6 mm. H: Quantification of liver metastases following tail vein injection of GDF15-expressing or silenced OMM1 cells (GDF15 shRNA#1 and shRNA#2).

Article Snippet: The effectiveness of blocking GDF15 on tube formation was assessed using an anti-GDF15 blocking antibody (ponsegromab: 120ng/ml, #HY-P99241, MedChemExpress, NJ, USA).

Techniques: Imaging, Injection, Staining, shRNA, Expressing

Journal: Cancer research

Article Title: GDF15 Reprograms the Microenvironment to Drive Liver Metastasis of Uveal Melanoma

doi: 10.1158/0008-5472.CAN-25-0536

Figure Lengend Snippet: A: H&E staining of livers from the eye to liver metastasis model, demonstrating fewer and smaller liver lesions following GDF15 shRNA silencing (shGDF15#1). B: Quantification of the size and number of liver metastases from A. C: IHC staining of liver metastases for fibronectin in MP41 tumors either expressing or with GDF15 silenced. D: Quantification of data from C. E: IHC staining of liver metastases from MP41 tumors for the ECM protein Collagen 1A1. F: Quantification of data from F. G: IHC staining of liver metastases for Ki67 in MP41 tumors either expressing or with GDF15 silenced. H: Quantification of data from G. I: IHC staining of liver metastases for the endothelial cell marker CD31 in MP41 tumors either expressing or with GDF15 silenced. J: Quantification of data from I.

Article Snippet: The effectiveness of blocking GDF15 on tube formation was assessed using an anti-GDF15 blocking antibody (ponsegromab: 120ng/ml, #HY-P99241, MedChemExpress, NJ, USA).

Techniques: Staining, shRNA, Immunohistochemistry, Expressing, Marker

Journal: Aging Cell

Article Title: Senescent Factors Suppress Innate Antiviral Immunity in Aged Mice via Two Distinct Mechanisms

doi: 10.1111/acel.70471

Figure Lengend Snippet: Neutralization of four SASP factors restores innate antiviral response in aged mice. (A) Serum levels of the indicated SASP factors in male C57BL/6 mice aged 3 m ( n = 5), 18 m ( n = 5), and 29 m ( n = 3) were measured by ELISA. (B–D) Eighteen‐month‐old male C57BL/6 mice were treated with control IgG ( n = 5) or with a combination of IL1Ra, anti‐IL6R, anti‐GDF15, and anti‐IGF1R ( n = 5) as described in the Methods section. (B) The mice were then infected intraperitoneally with HSV‐1 (1 × 10 7 PFU) for 6 h, or intranasally with H3N2 (1 × 10 6 PFU) for 24 h before measurements of serum IFNβ, CXCL10 and TNFα levels by ELISA. (C) The mice were then infected intraperitoneally with HSV‐1 (1 × 10 7 PFU), or intranasally with H3N2 (1 × 10 6 PFU) for 6 days before liver and lung tissues were collected for H&E staining analysis. Data were quantified using a semi‐quantitative 0–4 inflammation scoring system. (D) The mice were then infected intraperitoneally with HSV‐1 (1 × 10 7 PFU) for 6 h, or intranasally with H3N2 (1 × 10 6 PFU) for 24 h. The liver and lung tissues were subjected to immunohistochemical detection of HSV‐1 and H3N2 antigens. Quantitative data in (A, B) are presented as mean ± SD; each dot represents one mouse. H&E and IHC staining were quantified from five randomly selected non‐overlapping fields from two mice per group. Data are mean ± SD; each dot represents one field. One‐way ANOVA with Tukey's post hoc test. * p < 0.05; ns, not significant. N.D., not detected. Scale bars, 100 μm.

Article Snippet: To block SASP‐associated cytokine signaling, mice were injected intraperitoneally 24 h before infection with: anti‐IL6R (clone 15A7, MCE), 300 μg/mouse; anti‐GDF15 (Ponsegromab, Taoshu), 200 μg/mouse; and anti‐IGF1R (Ganitumab, Taoshu), 250 μg/mouse; and the natural IL‐1 receptor antagonistic protein IL1Ra (Raleukin, MCE), 500 μg/mouse.

Techniques: Neutralization, Enzyme-linked Immunosorbent Assay, Control, Infection, Staining, Immunohistochemical staining, Immunohistochemistry

Journal: iScience

Article Title: Association between elevated expression of GDF15/GFRAL and sarcopenia risk

doi: 10.1016/j.isci.2026.115023

Figure Lengend Snippet: The non-linear dose-response relationships between serum protein levels of GDF15 and GFRAL and sarcopenia risk (A) Serum GDF15 concentrations with age across three sarcopenia status groups; (B) The non-linear dose-response relationship between serum protein levels of GDF15 and sarcopenia risk.; (C) Serum GFRAL concentrations with age across three sarcopenia status groups; (D) The non-linear dose-response relationship between serum protein levels of GFRAL and sarcopenia risk. Data are presented as fitted values with 95% confidence intervals (CIs). See also .

Article Snippet: GDF15 (for immunohistochemical staining) , Proteintech , Cat No. 27455-1-AP.

Techniques:

Journal: iScience

Article Title: Association between elevated expression of GDF15/GFRAL and sarcopenia risk

doi: 10.1016/j.isci.2026.115023

Figure Lengend Snippet: Associations between serum protein levels of GDF15 and GFRAL and risks of sarcopenia and its phenotypes (A) Association of serum protein levels of GDF15 with risks of sarcopenia and its phenotypes; (B) Association of serum protein levels of GFRAL with risks of sarcopenia and its phenotypes. Model 0 was the crude model; Model 1 was adjusted for sex and age; Model 2 was further adjusted for Townsend deprivation index, educational attainment, smoking status, and alcohol consumption based on Model1. Abbreviations: CI, confidence interval. Data are presented as fitted values with 95% CIs. See also and , , and .

Article Snippet: GDF15 (for immunohistochemical staining) , Proteintech , Cat No. 27455-1-AP.

Techniques:

Journal: iScience

Article Title: Association between elevated expression of GDF15/GFRAL and sarcopenia risk

doi: 10.1016/j.isci.2026.115023

Figure Lengend Snippet: The effects of elevated GDF15 and GFRAL levels on sarcopenia (A) UMAP visualization of 11 annotated cell types in skeletal muscles from two frail mice and three control mice; (B) volcano plot showing differentially expressed genes in M2 macrophages from non-frail and frail muscle; (C) pathways involving GDF15 in M2 macrophages; (D–E) significantly up-regulated pathways of fibrosis-related genes between non-frail and frail muscle; (F) immunohistochemical staining for GDF15, with positive signals visualized as brown DAB precipitate. Scale bars, 200 μm.

Article Snippet: GDF15 (for immunohistochemical staining) , Proteintech , Cat No. 27455-1-AP.

Techniques: Muscles, Control, Immunohistochemical staining, Staining