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S100B drives glioblastoma invasion and migration through TGF‑β2‑mediated epithelial‑mesenchymal transition

  • Authors:
    • Xuemei Liao
    • Yuan Xu
    • Honghong Zhou
    • Qin Yi
    • Shifang Dong
    • Bin Tan
  • View Affiliations / Copyright

    Affiliations: Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 400014, P.R. China
    Copyright: © Liao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 20
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    Published online on: November 19, 2025
       https://doi.org/10.3892/or.2025.9025
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Abstract

Glioblastoma (GBM), the most common type of primary malignant brain tumor, is characterized by aggressive cancer cells that contribute to infiltrative growth, thus resulting in therapeutic challenges and a poor prognosis. To explore the molecular mechanisms underlying cell motility and to identify therapeutic targets that may intervene in tumor invasion, public databases were used to investigate the S100B expression profile and the prognosis of patients with tumors. The effects of S100B on a GBM cell line were assessed through lentiviral transduction, as well as cell viability, colony formation, 5‑ethynyl‑2'‑deoxyuridine‑based cell proliferation, cross‑scratch, and Transwell migration and invasion assays. In addition, a tumor xenograft model was constructed to analyze tumor growth in vivo. Reverse transcription-quantitative PCR, western blotting and immunofluorescence staining were utilized to explore the molecular biological mechanisms of the TGF‑β2‑induced epithelial‑mesenchymal transition (EMT) in the S100B‑downregulated group. The findings demonstrated that S100B was significantly upregulated in GBM samples and was strongly associated with patient prognosis. In vitro and in vivo experiments confirmed that downregulation of S100B effectively suppressed the proliferation and tumorigenicity, as well as decreased the invasive and migratory capabilities of LN229 glioblastoma cells. Further investigation revealed that the inhibition of S100B resulted in downregulation of TGF‑β2 expression and reversal of the EMT process. Notably, recombinant TGF‑β2 restored the cell motility and EMT capacities attenuated by the downregulation of S100B. In conclusion, the present study revealed that S100B may induce the invasion and migration of GBM cells through TGF‑β2‑induced EMT, providing novel insights and potential therapeutic targets for GBM.
View Figures

Figure 1

S100B is highly expressed in GBM. (A)
mRNA expression of S100B in different tumors was analyzed using the
HPA (https://www.proteinatlas.org/). (B)
Transcription levels of S100B in 34 types of tumor tissues and
their corresponding normal tissues were analyzed by SangerBOX
(http://sangerbox.com/). (C and D) GSE50161
dataset and Gene Expression Profiling Interactive Analysis of S100B
expression in GBM and normal tissues. (E and F) Immunohistochemical
staining of different tumor samples and representative images in
glioma with three different S100B antibodies; these data were
obtained from the HPA. *P<0.05, **P<0.01, ***P<0.001 and
****P<0.0001. GBM, glioblastoma multiforme; HPA, Human Protein
Atlas; TCGA, The Cancer Genome Atlas.

Figure 2

High expression of S100B is
associated with a poor prognosis. (A) Survival curve analysis of
the prognostic significance of the high and low mRNA expression
levels of S100B in glioma based on TGCA, Gene Expression Profiling
Interactive Analysis and SangerBOX databases. (B) Single-cell
sequencing data from TISCH analyzing the average expression of
S100B in different cell types across datasets. (C) Expression
distribution and relative expression levels of S100B in different
cell types in glioma tissue. TCGA, The Cancer Genome Atlas.

Figure 3

Lentiviral transduction-induced
knockdown of S100B in the LN229 glioblastoma multiforme cell line.
(A) Detection of S100B expression in LN229 cells by flow cytometry.
(B) Representative immunofluorescence images of S100B. Scale bars,
50 µm. (C) LN229 glioma cells were transduced with shS100B and
negative control vectors. (D and E) mRNA and protein levels of
S100B were analyzed by reverse transcription-quantitative PCR and
western blotting. Data are presented as the mean ± SEM. (F) S100B
expression in NC and shS100B groups was measured by
immunofluorescence staining. DAPI represents cell nuclei. Scale
bar, 50 µm. The statistical analyses of the relative mean
fluorescence intensity and the relative percentage of positive
cells were conducted. Data are presented as the mean ± SEM.
**P<0.01 and ****P<0.0001. shS100B, shRNA S100B; NC, negative
control.

Figure 4

S100B affects the proliferation of
LN229 cells and tumor growth in vivo. (A) Colony formation
assay assessed the proliferative capacity of NC and shS100B groups,
Scale bar, 500 µm. (B) DNA synthesis ability was assessed using the
EdU assays. Scale bar, 50 µm. (C) Cell Counting Kit-8 assay of
proliferation in NC and shS100B LN229 glioblastoma multiforme
cells. (D and E) Subcutaneous tumor model, tumor size and volume.
(F) Representative immunofluorescence staining images of S100B in
tumor tissue sections. DAPI represents cell nuclei. Statistical
analysis of relative mean fluorescence intensity of S100B was
performed. Data are presented as the mean ± SEM. Scale bar, 100 µm.
*P<0.05, **P<0.01, ***P<0.001 and ****P<0.0001.
shS100B, shRNA S100B; NC, negative control.

Figure 5

S100B affects the invasion and
migration of GBM cells via epithelial-mesenchymal transition. (A)
Detection of cell migration ability by cross-scratch assay; Scale
bar, 500 µm. Cell migration rate = Cell migration area/cross
scratch area. (B and C) Transwell assays analyzed the migratory and
invasive capacity of NC and shS100B GBM cells, Scale bar, 200 µm.
Relative proportion of migratory or invasive cells: Number of
migratory or invasive cells in shS100B group/number of migratory or
invasive cells in NC group. (D) Volcano plot showing the DEGs in
the NC and shS100B groups. (E) GO enrichment analysis of the
functions of downregulated DEG. (F) E-cadherin, N-cadherin and
vimentin expression in NC and shS100B LN229 cells were measured by
immunofluorescence staining. Blue represents cell nuclei, red
represents E-cadherin, N-cadherin and vimentin. Statistical
analysis of relative mean fluorescence intensity was performed.
Scale bar, 50 µm. Data are presented as the mean ± SEM. **P<0.01
and ****P<0.0001. GBM, glioblastoma multiforme; shS100B, shRNA
S100B; NC, negative control; DEGs, differentially expressed genes;
GO, Gene Ontology.

Figure 6

TGF-β2 induces epithelial-mesenchymal
transition and enhances the invasion and migration of glioblastoma
multiforme cells. (A) Relevant downregulated genes of the
mesenchyme morphogenesis pathway. (B and C) Expression of TGF-β2 in
NC and shS100B LN229 cells was analyzed by reverse
transcription-quantitative PCR and western blotting. (D)
Cross-scratch assay evaluated the migratory capacity of NC, shS100B
and shS100B + TGF-β2 groups, Scale bar, 500 µm. (E) Transwell assay
analyzed the migratory or invasive capacity of NC, shS100B and
shS100B + TGF-β2 groups; Scale bar, 200 µm. Relative proportion of
migratory or invasive cells: Number of migratory or invasive cells
in shS100B group or shS100B + TGF-β2 group/number of migrated or
invaded cells in NC group. (F) E-cadherin, N-cadherin and vimentin
were analyzed by immunofluorescence staining. Blue represents cell
nuclei, and red represents E-cadherin, N-cadherin and vimentin.
Scale bar, 50 µm. Data are presented as the mean ± SEM. *P<0.05,
**P<0.01, ***P<0.001 and ****P<0.0001. NC, negative
control; shS100B, shRNA S100B.
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Copy and paste a formatted citation
Spandidos Publications style
Liao X, Xu Y, Zhou H, Yi Q, Dong S and Tan B: S100B drives glioblastoma invasion and migration through TGF‑&beta;2‑mediated epithelial‑mesenchymal transition. Oncol Rep 55: 20, 2026.
APA
Liao, X., Xu, Y., Zhou, H., Yi, Q., Dong, S., & Tan, B. (2026). S100B drives glioblastoma invasion and migration through TGF‑&beta;2‑mediated epithelial‑mesenchymal transition. Oncology Reports, 55, 20. https://doi.org/10.3892/or.2025.9025
MLA
Liao, X., Xu, Y., Zhou, H., Yi, Q., Dong, S., Tan, B."S100B drives glioblastoma invasion and migration through TGF‑&beta;2‑mediated epithelial‑mesenchymal transition". Oncology Reports 55.1 (2026): 20.
Chicago
Liao, X., Xu, Y., Zhou, H., Yi, Q., Dong, S., Tan, B."S100B drives glioblastoma invasion and migration through TGF‑&beta;2‑mediated epithelial‑mesenchymal transition". Oncology Reports 55, no. 1 (2026): 20. https://doi.org/10.3892/or.2025.9025
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Spandidos Publications style
Liao X, Xu Y, Zhou H, Yi Q, Dong S and Tan B: S100B drives glioblastoma invasion and migration through TGF‑&beta;2‑mediated epithelial‑mesenchymal transition. Oncol Rep 55: 20, 2026.
APA
Liao, X., Xu, Y., Zhou, H., Yi, Q., Dong, S., & Tan, B. (2026). S100B drives glioblastoma invasion and migration through TGF‑&beta;2‑mediated epithelial‑mesenchymal transition. Oncology Reports, 55, 20. https://doi.org/10.3892/or.2025.9025
MLA
Liao, X., Xu, Y., Zhou, H., Yi, Q., Dong, S., Tan, B."S100B drives glioblastoma invasion and migration through TGF‑&beta;2‑mediated epithelial‑mesenchymal transition". Oncology Reports 55.1 (2026): 20.
Chicago
Liao, X., Xu, Y., Zhou, H., Yi, Q., Dong, S., Tan, B."S100B drives glioblastoma invasion and migration through TGF‑&beta;2‑mediated epithelial‑mesenchymal transition". Oncology Reports 55, no. 1 (2026): 20. https://doi.org/10.3892/or.2025.9025
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