Cross-platform analysis reveals cellular and molecular landscape of glioblastoma invasion

Chen, Ann T.; Xiao, Yang; Tang, Xiangjun; Baqri, Mehdi; Gao, Xingchun; Reschke, Melanie; Sheu, Wendy C.; Long, Gretchen; Zhou, Yu; Deng, Gang; Zhang, Shenqi; Deng, Yanxiang; Bai, Zhiliang; Kim, Dongjoo; Hüttner, Anita; Kunes, Russell; Günel, Murat; Moliterno, Jennifer; Saltzman, W. Mark; Fan, Rong; Zhou, Jiangbing

doi:10.1093/neuonc/noac186

Cited by 4 publications

(3 citation statements)

References 56 publications

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“…Additionally, we investigated the coordinated functions of multiple cell clusters and signaling pathways. Our study revealed that within the terminal differentiation stage of glioma tissue, a subpopulation of oligodendroglial cells exhibited the highest expression of CRYAB, which was associated with prognosis and confirmed by in vitro experiments ( 56 , 57 ). The knockdown of CRYAB in glioma cells resulted in the suppression of cell proliferation and migration, concomitant with the induction of apoptosis.…”

Section: Discussionsupporting

confidence: 78%

Single cell sequencing revealed the mechanism of CRYAB in glioma and its diagnostic and prognostic value

Cai,

Zhao,

et al. 2024

Front. Immunol.

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BackgroundWe explored the characteristics of single-cell differentiation data in glioblastoma and established prognostic markers based on CRYAB to predict the prognosis of glioblastoma patients. Aberrant expression of CRYAB is associated with invasive behavior in various tumors, including glioblastoma. However, the specific role and mechanisms of CRYAB in glioblastoma are still unclear.MethodsWe assessed RNA-seq and microarray data from TCGA and GEO databases, combined with scRNA-seq data on glioma patients from GEO. Utilizing the Seurat R package, we identified distinct survival-related gene clusters in the scRNA-seq data. Prognostic pivotal genes were discovered through single-factor Cox analysis, and a prognostic model was established using LASSO and stepwise regression algorithms. Moreover, we investigated the predictive potential of these genes in the immune microenvironment and their applicability in immunotherapy. Finally, in vitro experiments confirmed the functional significance of the high-risk gene CRYAB.ResultsBy analyzing the ScRNA-seq data, we identified 28 cell clusters representing seven cell types. After dimensionality reduction and clustering analysis, we obtained four subpopulations within the oligodendrocyte lineage based on their differentiation trajectory. Using CRYAB as a marker gene for the terminal-stage subpopulation, we found that its expression was associated with poor prognosis. In vitro experiments demonstrated that knocking out CRYAB in U87 and LN229 cells reduced cell viability, proliferation, and invasiveness.ConclusionThe risk model based on CRYAB holds promise in accurately predicting glioblastoma. A comprehensive study of the specific mechanisms of CRYAB in glioblastoma would contribute to understanding its response to immunotherapy. Targeting the CRYAB gene may be beneficial for glioblastoma patients.

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Section: Discussionsupporting

confidence: 78%

Single cell sequencing revealed the mechanism of CRYAB in glioma and its diagnostic and prognostic value

Cai,

Zhao,

et al. 2024

Front. Immunol.

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“…As a particular targeting ligand, in the current study we are interested in hyaluronic acid (HA, also referred to as hyaluronan), which can be conjugated onto liposome surface and utilized as a targeting moiety directed towards cancers 13 . HA binds to cell surface receptor CD44, which is overexpressed in several invasive tumors and can lead to enhanced nanoparticle uptake 14 – 16 .…”

Section: Introductionmentioning

confidence: 99%

Establishing a simple perfusion cell culture system for light-activated liposomes

Mäki-Mikola

Laurén

Uema

et al. 2023

Sci Rep

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The off-target effects of light-activated or targeted liposomes are difficult to distinguish in traditional well plate experiments. Additionally, the absence of fluid flow in traditional cell models can lead to overestimation of nanoparticle uptake. In this paper, we established a perfusion cell culture platform to study light-activated liposomes and determined the effect of flow on the liposomal cell uptake. The optimal cell culturing parameters for the A549 cells under flow conditions were determined by monitoring cell viability. To determine optimal liposome treatment times, particle uptake was measured with flow cytometry. The suitability of commercial QuasiVivo flow-chambers for near-infrared light activation was assessed with a calcein release study. The chamber material did not hinder the light activation and subsequent calcein release from the liposomes. Furthermore, our results show that the standard cell culturing techniques are not directly translatable to flow cultures. For non-coated liposomes, the uptake was hindered by flow. Interestingly, hyaluronic acid coating diminished the uptake differences between the flow and static conditions. The study demonstrates that flow affects the liposomal uptake by lung cancer cell line A549. The flow also complicates the cell attachment of A549 cells. Moreover, we show that the QuasiVivo platform is suitable for light-activation studies.

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“…Currently, the standard therapy of GBM is still operation for maximum resection of the tumor, accompanied by postoperative adjuvant radiotherapy and chemotherapy [ 2 ]. However, due to invasion, the postoperative recurrence rate is high, and the prognosis of patients is poor [ 3 ]. Temozolomide (TMZ) has been applied in clinical practice for > 20 years and is currently the first-line clinical chemotherapy drug [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Preclinical evaluation of Mito-LND, a targeting mitochondrial metabolism inhibitor, for glioblastoma treatment

Guo,

Wu,

Zhou

et al. 2023

J Transl Med

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Background Glioblastoma (GBM) is a brain tumor with the highest level of malignancy and the worst prognosis in the central nervous system. Mitochondrial metabolism plays a vital role in the occurrence and development of cancer, which provides critical substances to support tumor anabolism. Mito-LND is a novel small-molecule inhibitor that can selectively inhibit the energy metabolism of tumor cells. However, the therapeutic effect of Mito-LND on GBM remains unclear. Methods The present study evaluated the inhibitory effect of Mito-LND on the growth of GBM cells and elucidated its potential mechanism. Results The results showed that Mito-LND could inhibit the survival, proliferation and colony formation of GBM cells. Moreover, Mito-LND induced cell cycle arrest and apoptosis. Mechanistically, Mito-LND inhibited the activity of mitochondrial respiratory chain complex I and reduced mitochondrial membrane potential, thus promoting ROS generation. Importantly, Mito-LND could inhibit the malignant proliferation of GBM by blocking the Raf/MEK/ERK signaling pathway. In vivo experiments showed that Mito-LND inhibited the growth of GBM xenografts in mice and significantly prolonged the survival time of tumor-bearing mice. Conclusion Taken together, the current findings support that targeting mitochondrial metabolism may be as a potential and promising strategy for GBM therapy, which will lay the theoretical foundation for further clinical trials on Mito-LND in the future.

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Cross-platform analysis reveals cellular and molecular landscape of glioblastoma invasion

Cited by 4 publications

References 56 publications

Single cell sequencing revealed the mechanism of CRYAB in glioma and its diagnostic and prognostic value

Single cell sequencing revealed the mechanism of CRYAB in glioma and its diagnostic and prognostic value

Establishing a simple perfusion cell culture system for light-activated liposomes

Preclinical evaluation of Mito-LND, a targeting mitochondrial metabolism inhibitor, for glioblastoma treatment

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