Tumor microenvironment-preserving gliosarcoma organoids as an in vitro preclinical platform: a comparative analysis with glioblastoma models
Abstract Background Gliosarcoma (GS) is a rare variant of glioblastoma (GBM), characterized by biphasic glial and sarcomatous histology and poor prognosis. Despite its distinct clinical features, GS remains underrepresented in glioma research due to the lack of biologically faithful and experimental...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-08-01
|
| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-025-06952-y |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849235058512101376 |
|---|---|
| author | Junseong Park Dokyeong Kim Hyeon-Chun Park Minyoung Park Songzi Zhang Okcho Na Youn Soo Lee Minho Lee Stephen Ahn Yeun-Jun Chung |
| author_facet | Junseong Park Dokyeong Kim Hyeon-Chun Park Minyoung Park Songzi Zhang Okcho Na Youn Soo Lee Minho Lee Stephen Ahn Yeun-Jun Chung |
| author_sort | Junseong Park |
| collection | DOAJ |
| description | Abstract Background Gliosarcoma (GS) is a rare variant of glioblastoma (GBM), characterized by biphasic glial and sarcomatous histology and poor prognosis. Despite its distinct clinical features, GS remains underrepresented in glioma research due to the lack of biologically faithful and experimentally tractable models. Methods We established patient-derived gliosarcoma organoids (GSOs) from freshly resected tumors using a suspension culture system without enzymatic dissociation. Histological, molecular, and functional properties were evaluated using H&E staining, immunohistochemistry, whole-exome sequencing, 3D invasion assays, and single-cell RNA sequencing (scRNA-seq). Drug response assays were performed using temozolomide and ANA-12 (NTRK2 inhibitor). Results GSOs preserved key histological features, genetic alterations, and tumor microenvironmental cell populations from the original tumors. They stable growth and viability over extended culture periods and maintained integrity following cryopreservation and recovery, supporting their long-term utility. 3D invasion assays further revealed infiltrative behavior, consistent with the aggressive nature of GS. Histological and molecular analyses revealed that GSOs retained glial and mesenchymal differentiation, diverse non-malignant stromal cells, and case-specific somatic alterations. Comparative scRNA-seq revealed distinct transcriptional programs: GSOs were enriched for fibroblast-like and oligodendrocyte progenitor-like states, while glioblastoma organoids (GBOs) displayed astrocyte-like differentiation and high connectivity signatures. Functional assays confirmed consistent sensitivity of GSOs to temozolomide, and selective therapeutic response to NTRK2 inhibition was observed in the GSO harboring an NTRK2 alteration, supporting the utility for genomic-context-guided therapy. Conclusion Together, GSOs constitute a tractable and translationally relevant model that faithfully reflects the cellular complexity, genetic landscape, and tumor-specific heterogeneity. This model addresses a critical gap in GS biology and supports its integration into precision oncology. |
| format | Article |
| id | doaj-art-27a746f94a8a4653b517a17272dcf4cf |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-27a746f94a8a4653b517a17272dcf4cf2025-08-20T04:02:55ZengBMCJournal of Translational Medicine1479-58762025-08-0123111310.1186/s12967-025-06952-yTumor microenvironment-preserving gliosarcoma organoids as an in vitro preclinical platform: a comparative analysis with glioblastoma modelsJunseong Park0Dokyeong Kim1Hyeon-Chun Park2Minyoung Park3Songzi Zhang4Okcho Na5Youn Soo Lee6Minho Lee7Stephen Ahn8Yeun-Jun Chung9Cancer Evolution Research Center, College of Medicine, The Catholic University of KoreaPrecision Medicine Research Center, College of Medicine, The Catholic University of KoreaDepartment of Microbiology, College of Medicine, The Catholic University of KoreaDepartment of Microbiology, College of Medicine, The Catholic University of KoreaDepartment of Microbiology, College of Medicine, The Catholic University of KoreaDepartment of Microbiology, College of Medicine, The Catholic University of KoreaDepartment of Hospital Pathology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of KoreaDepartment of Life Science, Dongguk University-SeoulDepartment of Neurosurgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of KoreaPrecision Medicine Research Center, College of Medicine, The Catholic University of KoreaAbstract Background Gliosarcoma (GS) is a rare variant of glioblastoma (GBM), characterized by biphasic glial and sarcomatous histology and poor prognosis. Despite its distinct clinical features, GS remains underrepresented in glioma research due to the lack of biologically faithful and experimentally tractable models. Methods We established patient-derived gliosarcoma organoids (GSOs) from freshly resected tumors using a suspension culture system without enzymatic dissociation. Histological, molecular, and functional properties were evaluated using H&E staining, immunohistochemistry, whole-exome sequencing, 3D invasion assays, and single-cell RNA sequencing (scRNA-seq). Drug response assays were performed using temozolomide and ANA-12 (NTRK2 inhibitor). Results GSOs preserved key histological features, genetic alterations, and tumor microenvironmental cell populations from the original tumors. They stable growth and viability over extended culture periods and maintained integrity following cryopreservation and recovery, supporting their long-term utility. 3D invasion assays further revealed infiltrative behavior, consistent with the aggressive nature of GS. Histological and molecular analyses revealed that GSOs retained glial and mesenchymal differentiation, diverse non-malignant stromal cells, and case-specific somatic alterations. Comparative scRNA-seq revealed distinct transcriptional programs: GSOs were enriched for fibroblast-like and oligodendrocyte progenitor-like states, while glioblastoma organoids (GBOs) displayed astrocyte-like differentiation and high connectivity signatures. Functional assays confirmed consistent sensitivity of GSOs to temozolomide, and selective therapeutic response to NTRK2 inhibition was observed in the GSO harboring an NTRK2 alteration, supporting the utility for genomic-context-guided therapy. Conclusion Together, GSOs constitute a tractable and translationally relevant model that faithfully reflects the cellular complexity, genetic landscape, and tumor-specific heterogeneity. This model addresses a critical gap in GS biology and supports its integration into precision oncology.https://doi.org/10.1186/s12967-025-06952-yGliosarcomaPatient-derived organoidPrecision oncologySingle-cell RNA sequencingTumor microenvironment |
| spellingShingle | Junseong Park Dokyeong Kim Hyeon-Chun Park Minyoung Park Songzi Zhang Okcho Na Youn Soo Lee Minho Lee Stephen Ahn Yeun-Jun Chung Tumor microenvironment-preserving gliosarcoma organoids as an in vitro preclinical platform: a comparative analysis with glioblastoma models Journal of Translational Medicine Gliosarcoma Patient-derived organoid Precision oncology Single-cell RNA sequencing Tumor microenvironment |
| title | Tumor microenvironment-preserving gliosarcoma organoids as an in vitro preclinical platform: a comparative analysis with glioblastoma models |
| title_full | Tumor microenvironment-preserving gliosarcoma organoids as an in vitro preclinical platform: a comparative analysis with glioblastoma models |
| title_fullStr | Tumor microenvironment-preserving gliosarcoma organoids as an in vitro preclinical platform: a comparative analysis with glioblastoma models |
| title_full_unstemmed | Tumor microenvironment-preserving gliosarcoma organoids as an in vitro preclinical platform: a comparative analysis with glioblastoma models |
| title_short | Tumor microenvironment-preserving gliosarcoma organoids as an in vitro preclinical platform: a comparative analysis with glioblastoma models |
| title_sort | tumor microenvironment preserving gliosarcoma organoids as an in vitro preclinical platform a comparative analysis with glioblastoma models |
| topic | Gliosarcoma Patient-derived organoid Precision oncology Single-cell RNA sequencing Tumor microenvironment |
| url | https://doi.org/10.1186/s12967-025-06952-y |
| work_keys_str_mv | AT junseongpark tumormicroenvironmentpreservinggliosarcomaorganoidsasaninvitropreclinicalplatformacomparativeanalysiswithglioblastomamodels AT dokyeongkim tumormicroenvironmentpreservinggliosarcomaorganoidsasaninvitropreclinicalplatformacomparativeanalysiswithglioblastomamodels AT hyeonchunpark tumormicroenvironmentpreservinggliosarcomaorganoidsasaninvitropreclinicalplatformacomparativeanalysiswithglioblastomamodels AT minyoungpark tumormicroenvironmentpreservinggliosarcomaorganoidsasaninvitropreclinicalplatformacomparativeanalysiswithglioblastomamodels AT songzizhang tumormicroenvironmentpreservinggliosarcomaorganoidsasaninvitropreclinicalplatformacomparativeanalysiswithglioblastomamodels AT okchona tumormicroenvironmentpreservinggliosarcomaorganoidsasaninvitropreclinicalplatformacomparativeanalysiswithglioblastomamodels AT younsoolee tumormicroenvironmentpreservinggliosarcomaorganoidsasaninvitropreclinicalplatformacomparativeanalysiswithglioblastomamodels AT minholee tumormicroenvironmentpreservinggliosarcomaorganoidsasaninvitropreclinicalplatformacomparativeanalysiswithglioblastomamodels AT stephenahn tumormicroenvironmentpreservinggliosarcomaorganoidsasaninvitropreclinicalplatformacomparativeanalysiswithglioblastomamodels AT yeunjunchung tumormicroenvironmentpreservinggliosarcomaorganoidsasaninvitropreclinicalplatformacomparativeanalysiswithglioblastomamodels |