ArticleJournal of translational medicine2025
Spatial transcriptomics and multi-omics reveal relapse and resistance mechanisms of EndMT-derived CAFs mediated by TNC and FLNC in glioblastoma.
Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- In Situ Photo‑Crosslinked Functional Bilayer Hydrogel Modulates Local Microenvironment and Remyelination After Optic Nerve Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Invasive Margin of Glioblastoma as a Molecular Ecosystem: Spatial Heterogeneity, Tumor-Host Interactions, and Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Filamin C activates MAPK/ERK signaling to facilitate epithelial-mesenchymal transition in bladder cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Leveraging single-cell and spatial omics for brain tumour insights to improve therapeutic strategies.Molecular brain · 2026Review
- Astrocytes in neuroinflammation and brain cancer.Molecular biomedicine · 2026Review
- Pericyte-derived cancer-associated fibroblasts correlate with poor survival and are enriched after chemoradiotherapy in glioblastoma.PloS one · 2026Article
- Harnessing transcriptomics for discovery of natural products to overcome acquired cancer resistance.Archives of pharmacal research · 2026Review
- Cross-talk between cancer-associated fibroblasts and dormant cancer cells: current status and promising therapeutic potential.Cancer cell international · 2025Review
- Review
- Second harmonic generation for brain imaging: pathology-related studies.Biophysical reviews · 2025Article
- Deciphering the Tenascin-C Nexus: A Comprehensive Review of Its Involvement in Chronic Respiratory Diseases.Pathophysiology : the official journal of the International Society for Pathophysiology · 2025Review
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12 authors.
Funding
Abstract
backgroundChemoresistance and recurrence following treatment are the greatest impediments to the prognosis of glioblastoma (GBM). Increasing evidence indicates that cancer-associated fibroblasts (CAFs) play a significant role in the progression of glioblastoma. Nevertheless, the role and source of CAFs in recurrent and chemotherapy-resistant GBMs still remain ambiguous.
methodsSpatial transcriptome (ST) sequencing was conducted on the tissue microarray encompassing primary and recurrent glioma samples in order to characterize the cellular composition. Subsequently, the infiltration of CAFs in our formerly established in vivo temozolomide (TMZ)-resistant model was inspected through immunohistochemical staining. Additionally, we carried out RNA-seq and label-free quantitation (LFQ) proteomics on HCMECs co-cultured with TMZ-sensitive (TMZ-S) or TMZ-resistant (TMZ-R) cells to explore the mechanism.
resultsThis investigation revealed that CAFs and astrocytes are enriched in recurrent GBM, and this phenotype is associated with the expression of extracellular matrix (ECM) proteins associated with COL1A1 and FN1 deposition. Further investigations revealed that tenascin-C (TNC) and filamin C (FLNC), which potentially mediate endothelial-to-mesenchymal transition (EndMT), are the predominant factors that induce the deposition of ECM proteins in the resistance-promoting microenvironment. Additionally, the natural product punicalin (PNC) was found to downregulate EndMT-related proteins, multidrug resistance-associated membrane proteins, and collagen-related proteins by targeting TNC and FLNC, thereby increasing the susceptibility of temozolomide (TMZ)-resistant cells to chemotherapeutic agents both in vitro and in vivo.
conclusionThese discoveries indicate that TNC and FLNC induced EndMT was a key resource of CAFs and targeting TNC and FLNC to inhibit EndMT and the collagen pathway is a promising tactic for reversing drug resistance in tumours. The development of combined chemotherapeutic strategies based on the features of tumour microenvironment endothelial cells and ECM deposition has high potential clinical value in increasing the efficacy of tumour treatment.
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