High density is a property of slow-cycling and treatment-resistant human glioblastoma cells

Sabelström, Hanna; Quigley, David A.; Fenster, Trenten; Foster, Daniel J.; Fuchshuber, Clara A.M.; Saxena, Supna; Yuan, Edith; Li, Nan; Paterno, Francesca; James, C. David; Norling, Börje; Berger, Mitchel S.; Persson, Anders I.

doi:10.1016/j.yexcr.2019.03.003

Cited by 16 publications

(12 citation statements)

References 56 publications

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“…This supports the notion that tumor regrowth is more aggressive after surgical resection of primary glioblastoma tumors [45,46], possibly because resection-induced astrocyte injury can support faster growth [46]. Additionally, space and oxygen can promote tumor regrowth [47,48,49], while a stronger immune response after resection would reduce it. In this regard, our large range of tumor cell survival rates might reflect the different balances between these (and other) parameters.…”

Section: Tumor Cell Survival At the Transition From Primary To Recurrent Tumorsupporting

confidence: 75%

Time-resolved, integrated analysis of clonally evolving genomes

Legrand

Andriantsoa

Lichter

et al. 2021

Preprint

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Clonal genome evolution is a key aspect for parthenogenetic species and cancer. While many studies describe precise landscapes of clonal evolution in cancer, few studies determine the underlying evolutionary parameters from molecular data, and fewer integrate theory with data. We derived theoretical results linking mutation rate, time, expansion dynamics, transition to recurrence, and survival. With this, we inferred time-resolved estimates of evolutionary parameters from mutation accumulation, mutational signatures and selection. Using this framework we traced the speciation of the rapidly emerging and invasive marbled crayfish to a time window between 1947 and 1996, which is consistent with biological records. In glioblastoma samples, we determined tumor expansion patterns, and tumor cell survival ratio at resection. Interestingly, our results suggest that the expansion pattern in the primary tumor is predictive of the progress and time to recurrence. In addition, tumor cell survival was always higher after resection and was associated with the expansion pattern and time to recurrence. We further observed selection events in a subset of tumors, with longer and purifying-only selection phases in recurrent tumors. In conclusion, our framework allowed a time-resolved, integrated analysis of key parameters in clonally evolving genomes, and provided novel insights into the evolutionary age of marbled crayfish and the progression of glioblastoma.

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Section: Tumor Cell Survival At the Transition From Primary To Recurrent Tumorsupporting

confidence: 75%

Time-resolved, integrated analysis of clonally evolving genomes

Legrand

Andriantsoa

Lichter

et al. 2021

Preprint

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“…Due to the infiltration of glioma cells to surrounding brain tissue and poor permeability of the blood–brain barrier to chemotherapy drugs,9 it is still difficult to completely remove the tumor even using the current advanced microsurgical techniques 10,11. Thereby leading to high resistance and tolerance of glioma cells to treatment 12,13. Therefore, the challenge in the field of nerve tumor therapy is to find new treatment methods, which can effectively inhibit the malignant biological characteristics of glioma, thus prolonging the survival time of patients and improving their quality of life.…”

Section: Introductionmentioning

confidence: 99%

<p>LncRNA RHPN1-AS1 Targeting miR-625/REG3A Promotes Cell Proliferation And Invasion Of Glioma Cells</p>

Cui¹,

Su²,

Li³

et al. 2019

OTT

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IntroductionGlioma arises from the proliferation of neuroglial cells differentiated from the ectoderm. Evidence has confirmed that differentially expressed long non-coding RNAs (lncRNAs) may be involved in the development and progression of various tumors. The present study aimed to explore the biological function of lncRNA RHPN1-AS1 in glioma.Materials and methodsThe expressions of RHPN1-AS1 in glioma tissues and cells were examined using RT-PCR. Colony formation assay, MTT assay, wound healing assay and transwell assay were performed to detect cell cloning efficiency, proliferation, migration and invasion of glioma cells, respectively. Western blot was applied to assess the expression levels of migration-related and invasion-related proteins. Online bioinformatic tools and luciferase reporter assay were, respectively, employed to predict and verify the downstream target microRNA/gene of RHPN1-AS1.ResultsRHPN1-AS1 was up-regulated in glioma tissues and cells. The cell proliferation, migration and invasion of glioma were inhibited when the expression of RHPN1-AS1 was down-regulated in glioma cells. The expressions of migration-related and invasion-related proteins were also suppressed in siRHPN1-AS1 groups. Furthermore, we predicted and verified that RHPN1-AS1 was directly targeted to miR-625-5p/REG3A. Our study demonstrated that the knockdown of RHPN1-AS1 inhibited the proliferation, migration and invasion activity of glioma cells via regulating miR-625-5p/REG3A expression.ConclusionThe results revealed that the lncRNA RHPN1-AS1 may be a molecular target in glioma therapy.

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“…An interesting paradigm shift through recent studies have shown that intratumoral heterogeneity is composed of both fast-cycling cells, which follow the Warburg effect, and slow-cycling cells that utilize oxidative phosphorylation while leveraging other metabolites, such as fatty acid metabolic precursors, for survival [46,47]. Slow-cycling cells possess enhanced migratory potential, stemness, proliferation, and treatment resistance compared with fast-cycling cells, especially at high densities [46,48]. Similarly, another study examining metabolic stress in reprogramming of lipid metabolism, found that exogenous loading of low-density lipoproteins (LDL) in hypoxic conditions in vitro resulted in a lipid-loaded phenotype similar to GBM patient tumors in hypoxic regions [49].…”

Section: Cancer-metabolic Reprogrammingmentioning

confidence: 99%

Modulating Microenvironments for Treating Glioblastoma

Roberts

Munson

2020

Curr. Tissue Microenviron. Rep.

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Purpose of Review This review focuses on the development and progression of glioblastoma through the brain and glioma microenvironment. Specifically, we highlight how the tumor microenvironment contributes to the hallmarks of cancer in hopes of offering novel therapeutic options and tools to target. Recent Findings The hallmarks of cancer represent elements of cancer that contribute to the disease's malignancy, yet elements within the brain tumor microenvironment, such as other cellular types as well as biochemical and biophysical cues that can each uniquely affect tumor cells, have not been well-described in this context and serve as potential targets for modulation. Summary Here, we highlight how the brain tumor microenvironment contributes to the progression and therapeutic response of tumor cells. Specifically, we examine these contributions through the lens of Hanahan and Weinberg's "Hallmarks of Cancer" in order to identify potential novel targets within the brain that may offer a means to treat brain cancers, including the deadliest form of brain cancer, glioblastoma.

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High density is a property of slow-cycling and treatment-resistant human glioblastoma cells

Cited by 16 publications

References 56 publications

Time-resolved, integrated analysis of clonally evolving genomes

Time-resolved, integrated analysis of clonally evolving genomes

<p>LncRNA RHPN1-AS1 Targeting miR-625/REG3A Promotes Cell Proliferation And Invasion Of Glioma Cells</p>

Modulating Microenvironments for Treating Glioblastoma

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