Association of glioma CD44 expression with glial dynamics in the tumour microenvironment and patient prognosis

Du, Zhanxin; Wang, Yaqing; Liang, Jiaqi; S, Gao; Cai, Xiaoying; Yu, Yu; Qi, Zhihui; Li, Jing; Xie, Yubin; Wang, Zhongxing

doi:10.1016/j.csbj.2022.09.003

Cited by 9 publications

(8 citation statements)

References 95 publications

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“…High CD44 expression significantly correlates with the expression of drug resistance and metastasis-associated genes and generally occurs during an epithelial-mesenchymal transition [ 42 ]. According to the immunohistochemical analysis on tumor sections, CD44+ cells range from 60% to 90% of the population in glioma [ 43 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

Nanomechanical Signatures in Glioma Cells Depend on CD44 Distribution in IDH1 Wild-Type but Not in IDH1R132H Mutant Early-Passage Cultures

Shmelev

Farniev

Shved

et al. 2023

IJMS

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Atomic force microscopy (AFM) recently burst into biomedicine, providing morphological and functional characteristics of cancer cells and their microenvironment responsible for tumor invasion and progression, although the novelty of this assay needs to coordinate the malignant profiles of patients’ specimens to diagnostically valuable criteria. Applying high-resolution semi-contact AFM mapping on an extended number of cells, we analyzed the nanomechanical properties of glioma early-passage cell cultures with a different IDH1 R132H mutation status. Each cell culture was additionally clustered on CD44+/− cells to find possible nanomechanical signatures that differentiate cell phenotypes varying in proliferative activity and the characteristic surface marker. IDH1 R132H mutant cells compared to IDH1 wild-type ones (IDH1wt) characterized by two-fold increased stiffness and 1.5-fold elasticity modulus. CD44+/IDH1wt cells were two-fold more rigid and much stiffer than CD44-/IDH1wt ones. In contrast to IDH1 wild-type cells, CD44+/IDH1 R132H and CD44-/IDH1 R132H did not exhibit nanomechanical signatures providing statistically valuable differentiation of these subpopulations. The median stiffness depends on glioma cell types and decreases according to the following manner: IDH1 R132H mt (4.7 mN/m), CD44+/IDH1wt (3.7 mN/m), CD44-/IDH1wt (2.5 mN/m). This indicates that the quantitative nanomechanical mapping would be a promising assay for the quick cell population analysis suitable for detailed diagnostics and personalized treatment of glioma forms.

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Section: Discussionmentioning

confidence: 99%

Nanomechanical Signatures in Glioma Cells Depend on CD44 Distribution in IDH1 Wild-Type but Not in IDH1R132H Mutant Early-Passage Cultures

Shmelev

Farniev

Shved

et al. 2023

IJMS

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“…This finding supports observations that elevated ECM-receptor signaling, such as CD44 activation, can promote more aggressive and therapy resistant phenotypes in GBM and activate immune cells that facilitate disease progression. 27,[40][41][42][43] This is to our knowledge the first report on the heterogeneous biophysical characteristics of the aceullar human GBM TME in patient-matched samples. Limitations of this study include a small sample size, semi-quantitative approaches in image characterization, and a lack of omics-level analysis.…”

Section: Biophysical Characteristicmentioning

confidence: 99%

The prognostic effect of mechanical, ultrastructural, and ECM signatures in glioblastoma core and rim

Mahaffey,

Fowler,

Lung

et al. 2024

APL Bioengineering

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Glioblastoma (GBM) is a highly invasive, aggressive brain cancer that carries a median survival of 15 months and is resistant to standard therapeutics. Recent studies have demonstrated that intratumoral heterogeneity plays a critical role in promoting resistance by mediating tumor adaptation through microenvironmental cues. GBM can be separated into two distinct regions—a core and a rim, which are thought to drive specific aspects of tumor evolution. These differences in tumor progression are regulated by the diverse biomolecular and biophysical signals in these regions, but the acellular biophysical characteristics remain poorly described. This study investigates the mechanical and ultrastructural characteristics of the tumor extracellular matrix (ECM) in patient-matched GBM core and rim tissues. Seven patient-matched tumor core and rim samples and one non-neoplastic control were analyzed using atomic force microscopy, scanning electron microscopy, and immunofluorescence imaging to quantify mechanical, ultrastructural, and ECM composition changes. The results reveal significant differences in biophysical parameters between GBM core, rim, and non-neoplastic tissues. The GBM core is stiffer, denser, and is rich in ECM proteins hyaluronic acid and tenascin-C when compared to tumor rim and non-neoplastic tissues. These alterations are intimately related and have prognostic effect with stiff, dense tissue correlating with longer progression-free survival. These findings reveal new insights into the spatial heterogeneity of biophysical parameters in the GBM tumor microenvironment and identify a set of characteristics that may correlate with patient prognosis. In the long term, these characteristics may aid in the development of strategies to combat therapeutic resistance.

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“…Recent studies have suggested that high expression of CD44 in glioma cells is associated with the mesenchymal transition, increased recruitment of macrophages and reduced survival time in glioma patients [ 179 ]. Based on CIBERSORT analysis, Du and colleagues [ 180 ] have proposed that CD44+ glioma cells communicate with pro-inflammatory microglia-derived brain macrophages through SPP1-CD44 signalling. Interestingly, tumour-associated astrocytes increase the migratory ability of glioma cells via up-regulation of glioma cell CD44.…”

Section: Factors That Contribute To the Mesenchymal Transition Of Mal...mentioning

confidence: 99%

“…Interestingly, tumour-associated astrocytes increase the migratory ability of glioma cells via up-regulation of glioma cell CD44. They also promote recruitment of pro-inflammatory macrophages which may play a role in inducing glioma stemness via the SPP1-CD44 pathway [ 180 ]. This observation is in line with earlier findings showing that high expression of Gpnmb and Spp1 is detected in both murine and human glioma-associated microglia/macrophages and is associated with reduced survival time in patients with GBM [ 181 ].…”

Section: Factors That Contribute To the Mesenchymal Transition Of Mal...mentioning

confidence: 99%

Microglia and Brain Macrophages as Drivers of Glioma Progression

Zheng

Graeber

2022

IJMS

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Evidence is accumulating that the tumour microenvironment (TME) has a key role in the progression of gliomas. Non-neoplastic cells in addition to the tumour cells are therefore finding increasing attention. Microglia and other glioma-associated macrophages are at the centre of this interest especially in the context of therapeutic considerations. New ideas have emerged regarding the role of microglia and, more recently, blood-derived brain macrophages in glioblastoma (GBM) progression. We are now beginning to understand the mechanisms that allow malignant glioma cells to weaken microglia and brain macrophage defence mechanisms. Surface molecules and cytokines have a prominent role in microglia/macrophage-glioma cell interactions, and we discuss them in detail. The involvement of exosomes and microRNAs forms another focus of this review. In addition, certain microglia and glioma cell pathways deserve special attention. These “synergistic” (we suggest calling them “Janus”) pathways are active in both glioma cells and microglia/macrophages where they act in concert supporting malignant glioma progression. Examples include CCN4 (WISP1)/Integrin α6β1/Akt and CHI3L1/PI3K/Akt/mTOR. They represent attractive therapeutic targets.

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Association of glioma CD44 expression with glial dynamics in the tumour microenvironment and patient prognosis

Cited by 9 publications

References 95 publications

Nanomechanical Signatures in Glioma Cells Depend on CD44 Distribution in IDH1 Wild-Type but Not in IDH1R132H Mutant Early-Passage Cultures

Nanomechanical Signatures in Glioma Cells Depend on CD44 Distribution in IDH1 Wild-Type but Not in IDH1R132H Mutant Early-Passage Cultures

The prognostic effect of mechanical, ultrastructural, and ECM signatures in glioblastoma core and rim

Microglia and Brain Macrophages as Drivers of Glioma Progression

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