Force-mediated proinvasive matrix remodeling driven by tumor-associated mesenchymal stem-like cells in glioblastoma

Lim, Eun Jung; Suh, Yongjoon; Kim, Seungmo; Kang, Seok‐Gu; Lee, Su Jae

doi:10.5483/bmbrep.2018.51.4.185

Cited by 22 publications

(26 citation statements)

References 34 publications

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“…The concept of tumor cell traps, which emerged from the ecological trap strategy, was developed for brain tumors as a means of attracting the residual cancer cells surrounding the surgical cavity to the cavity, where they are trapped within a biomaterial support that can be targeted by treatment, such as stereotactic radiosurgery [ 46 , 47 ]. As indicated above, we and others have shown that GASCs increase the invasiveness of GB cells [ 10 , 12 , 13 , 17 , 24 , 25 ]. Based on this knowledge, we used GASC-conditioned medium as a source of chemoattractants to load the trap.…”

Section: Gascs: a Future Treatment Target Or Therapeutic Tool?mentioning

confidence: 80%

“…GASCs have been isolated from primary cultures of cells from mouse orthotopic transplantation tumor models [ 7 , 8 ], human low-grade gliomas (LGGs), human high-grade gliomas (HGGs) [ 2 , 3 , 4 , 5 , 6 , 8 , 9 , 10 , 11 , 12 , 13 , 15 , 18 , 19 , 20 , 26 ], and the peritumoral region of glioblastomas (GBs) [ 22 , 23 , 24 , 25 ] ( Table 1 ). Cultured GASCs are spindle-shaped, adherent in culture, can be subcultured many times, and express the mesenchymal surface markers CD73, CD90, and CD105.…”

Section: General Characteristics Of Gascsmentioning

confidence: 99%

“…GASCs have also been shown to boost the invasiveness of GB cells [ 10 , 12 , 13 , 17 , 23 , 25 ]. Force-mediated ECM remodeling through CCL2/JAK1/MLC2 signaling and the secretion of CXCL14 and C5a may be drivers of the glioma invasion mediated by GASCs [ 10 , 12 , 13 , 25 ].…”

Section: Functions Of Gascsmentioning

confidence: 99%

“…Blood vessels, immune cells, and neuroglial cells are classically considered to be the major cellular components of the microenvironment of gliomas [ 1 ], but there is recent evidence to suggest that gliomas also harbor stromal cells with the characteristics of mesenchymal stem cells (MSCs) and cancer-associated fibroblasts (CAFs). These stromal cells have been given various names in previous studies: glioma-associated human MSCs (GA-hMSCs) [ 2 , 3 , 4 ], glioma-associated MSCs or glioblastoma-derived MSCs (gbMSCs) [ 5 , 6 ], glioma stroma-MSCs (GS-MSCs) [ 7 ], brain tumor-derived MSCs (BT-MSCs) [ 8 ], mesenchymal stem-like cells (MSLCs) [ 9 , 10 , 11 ], tumor MSCLs (tMSLCs) [ 12 , 13 , 14 , 15 ], glioma stromal MSLCs (GS-MSLCs) [ 16 ], CAF-like cells [ 17 ], glioblastoma-associated stromal cells or glioma-associated stem cells (GASCs) [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. Here, we will call them GASCs (glioma-associated stromal cells), and we provide an overview of the principal studies on these cells to date.…”

Section: Introductionmentioning

confidence: 99%

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Mesenchymal Stromal-Like Cells in the Glioma Microenvironment: What Are These Cells?

Clavreul

Meneï

2020

Cancers

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The glioma microenvironment is a critical regulator of tumor progression. It contains different cellular components such as blood vessels, immune cells, and neuroglial cells. It also contains non-cellular components, such as the extracellular matrix, extracellular vesicles, and cytokines, and has certain physicochemical properties, such as low pH, hypoxia, elevated interstitial pressure, and impaired perfusion. This review focuses on a particular type of cells recently identified in the glioma microenvironment: glioma-associated stromal cells (GASCs). This is just one of a number of names given to these mesenchymal stromal-like cells, which have phenotypic and functional properties similar to those of mesenchymal stem cells and cancer-associated fibroblasts. Their close proximity to blood vessels may provide a permissive environment, facilitating angiogenesis, invasion, and tumor growth. Additional studies are required to characterize these cells further and to analyze their role in tumor resistance and recurrence.

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Section: Gascs: a Future Treatment Target Or Therapeutic Tool?mentioning

confidence: 80%

Section: General Characteristics Of Gascsmentioning

confidence: 99%

Section: Functions Of Gascsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mesenchymal Stromal-Like Cells in the Glioma Microenvironment: What Are These Cells?

Clavreul

Meneï

2020

Cancers

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“…GA‐MSC modifications of GBM microenvironment are also dependent on CCL2 release, which mediates the activation of JAK1 to regulate actin‐myosin contractility and TME and tissue mechanical stiffness needed to promote the motility of tumor cells. Therefore, GA‐MSC contribute to ECM remodeling modifying GBM stiffness similarly to what CAFs do in carcinomas 107 . Recently, the same authors reported that C5a released by GA‐MSCs increases ZEB1 levels in GBM cells through the activation of C5aR1 and p38 MAPK signaling, promoting the invasiveness of GBM without modifying growth rate in vitro.…”

Section: Crosstalk Between Msc and Gbm Cells: Direct And Indirect Intmentioning

confidence: 87%

Cross talk between mesenchymal and glioblastoma stem cells: Communication beyond controversies

Bajetto

Thellung

Dellacasagrande

et al. 2020

Stem Cells Translational Medicine

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Mesenchymal stem cells (MSCs) can be isolated from bone marrow or other adult tissues (adipose tissue, dental pulp, amniotic fluid, and umbilical cord). In vitro, MSCs grow as adherent cells, display fibroblast-like morphology, and self-renew, undergoing specific mesodermal differentiation. High heterogeneity of MSCs from different origin, and differences in preparation techniques, make difficult to uniform their functional properties for therapeutic purposes. Immunomodulatory, migratory, and differentiation ability, fueled clinical MSC application in regenerative medicine, whereas beneficial effects are currently mainly ascribed to their secretome and extracellular vesicles. MSC translational potential in cancer therapy exploits putative anti-tumor activity and inherent tropism toward tumor sites to deliver cytotoxic drugs. However, controversial results emerged evaluating either the therapeutic potential or homing efficiency of MSCs, as both antitumor and protumor effects were reported. Glioblastoma (GBM) is the most malignant brain tumor and its development and aggressive nature is sustained by cancer stem cells (CSCs) and the identification of effective therapeutic is required. MSC dualistic action, tumor-promoting or tumor-targeting, is dependent on secreted factors and extracellular vesicles driving a complex cross talk between MSCs and GBM CSCs. Tumor-tropic ability of MSCs, besides providing an alternative therapeutic approach, could represent a tool to understand the biology of GBM CSCs and related paracrine mechanisms, underpinning MSC-GBM interactions. In this review, recent findings on the complex nature of MSCs will be highlighted, focusing on their elusive impact on GBM progression and aggressiveness by direct cell-cell interaction and via secretome, also facing the perspectives and challenges in treatment strategies.

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Glioblastoma‐educated mesenchymal stem‐like cells promote glioblastoma infiltration via extracellular matrix remodelling in the tumour microenvironment

Kim

Lim

Yoo

et al. 2022

Clinical & Translational Med

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Background The biological function of mesenchymal stem‐like cells (MSLCs), a type of stromal cells, in the regulation of the tumour microenvironment is unclear. Here, we investigated the molecular mechanisms underlying extracellular matrix (ECM) remodelling and crosstalk between MSLCs and glioblastomas (GBMs) in tumour progression. Methods In vitro and in vivo co‐culture systems were used to analyze ECM remodelling and GBM infiltration. In addition, clinical databases, samples from patients with GBM and a xenografted mouse model of GBM were used. Results Previous studies have shown that the survival of patients with GBM from whom MSLCs could be isolated is substantially shorter than that of patients from whom MSLCs could not be isolated. Therefore, we determined the correlation between changes in ECM‐related gene expression in MSLC‐isolatable patients with that in MSLC non‐isolatable patients using gene set enrichment analysis (GSEA). We found that lysyl oxidase (LOX) and COL1A1 expressions increased in MSLCs via GBM‐derived clusters of differentiation 40 ligand (CD40L). Mechanistically, MSLCs are reprogrammed by the CD40L/CD40/NFκB2 signalling axis to build a tumour infiltrative microenvironment involving collagen crosslinking. Importantly, blocking of CD40L by a neutralizing antibody‐suppressed LOX expression and ECM remodelling, decreasing GBM infiltration in mouse xenograft models. Clinically, high expression of CD40L, clusters of differentiation 40 (CD40) and LOX correlated with poor survival in patients with glioma. This indicated that GBM‐educated MSLCs promote GBM infiltration via ECM remodelling in the tumour microenvironment. Conclusion Our findings provide mechanistic insights into the pro‐infiltrative tumour microenvironment produced by GBM‐educated MSLCs and highlight a potential therapeutic target that can be used for suppressing GBM infiltration.

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Force-mediated proinvasive matrix remodeling driven by tumor-associated mesenchymal stem-like cells in glioblastoma

Cited by 22 publications

References 34 publications

Mesenchymal Stromal-Like Cells in the Glioma Microenvironment: What Are These Cells?

Mesenchymal Stromal-Like Cells in the Glioma Microenvironment: What Are These Cells?

Cross talk between mesenchymal and glioblastoma stem cells: Communication beyond controversies

Glioblastoma‐educated mesenchymal stem‐like cells promote glioblastoma infiltration via extracellular matrix remodelling in the tumour microenvironment

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