Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Behaviors of Glioblastoma Cells in in Vitro Microenvironments.

ABSTRACT: Glioblastoma (GBM) is the most malignant and highly aggressive brain tumor. In this study, four types of typical GBM cell lines (LN229, SNB19, U87, U251) were cultured in a microfabricated 3-D model to study their in vitro behaviors. The 3-D in vitro model provides hollow micro-chamber arrays containing a natural collagen interface and thus allows the GBM cells to grow in the 3-D chambers. The GBM cells in this model showed specific properties on the aspects of cell morphology, proliferation, migration, and invasion, some of which were rarely observed before. Furthermore, how the cells invaded into the surrounding ECM and the corresponding specific invasion patterns were observed in details, implying that the four types of cells have different features during their development in cancer. This complex in vitro model, if applied to patient derived cells, possesses the potential of becoming a clinically relevant predictive model.

SUBMITTER: Diao W

PROVIDER: S-EPMC6331579 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Behaviors of Glioblastoma Cells in in Vitro Microenvironments.

Diao Wenwen W Tong Xuezhi X Yang Cheng C Zhang Fengrong F Bao Chun C Chen Hao H Liu Liyu L Li Ming M Ye Fangfu F Fan Qihui Q Wang Jiangfei J Ou-Yang Zhong-Can ZC

Scientific reports 20190114 1

Glioblastoma (GBM) is the most malignant and highly aggressive brain tumor. In this study, four types of typical GBM cell lines (LN229, SNB19, U87, U251) were cultured in a microfabricated 3-D model to study their in vitro behaviors. The 3-D in vitro model provides hollow micro-chamber arrays containing a natural collagen interface and thus allows the GBM cells to grow in the 3-D chambers. The GBM cells in this model showed specific properties on the aspects of cell morphology, proliferation, mi ...[more]

PMID: 30643153

Similar Datasets

Collective behaviors of Drosophila-derived retinal progenitors in controlled microenvironments.

Project description:Collective behaviors of retinal progenitor cells (RPCs) are critical to the development of neural networks needed for vision. Signaling cues and pathways governing retinal cell fate, migration, and functional organization are remarkably conserved across species, and have been well-studied using Drosophila melanogaster. However, the collective migration of heterogeneous groups of RPCs in response to dynamic signaling fields of development remains incompletely understood. This is in large part because the genetic advances of seminal invertebrate models have been poorly complemented by in vitro cell study of its visual development. Tunable microfluidic assays able to replicate the miniature cellular microenvironments of the developing visual system provide newfound opportunities to probe and expand our knowledge of collective chemotactic responses essential to visual development. Our project used a controlled, microfluidic assay to produce dynamic signaling fields of Fibroblast Growth Factor (FGF) that stimulated the chemotactic migration of primary RPCs extracted from Drosophila. Results illustrated collective RPC chemotaxis dependent on average size of clustered cells, in contrast to the non-directional movement of individually-motile RPCs. Quantitative study of these diverse collective responses will advance our understanding of retina developmental processes, and aid study/treatment of inherited eye disease. Lastly, our unique coupling of defined invertebrate models with tunable microfluidic assays provides advantages for future quantitative and mechanistic study of varied RPC migratory responses.

| S-EPMC6910854 | biostudies-literature

Immune microenvironments differ in immune characteristics and outcome of glioblastoma multiforme.

Project description:Understanding the interactions between tumors and the host immune system holds great promise to uncover biomarkers for targeted therapies, predict the prognosis of patients and guide clinical treatment. However, the immune signatures of glioblastoma multiforme (GBM) remain largely unstudied in terms of systematic analyses. We aimed to classify GBM samples according to immune-related genes and complement the existing immunotherapy system knowledge. In this study, we designed a strategy to identify 3 immune subtypes representing 3 different immune microenvironments (M1-M3) and associated with prognosis. The 3 subtypes were significantly different in terms of specific immune characteristics (immune cell subpopulations, immune responses, immune cells, and checkpoint gene interactions). In additional, copy number variations and methylation changes were identified that correlated with genes related to a worse prognosis subtype in the microenvironment. More importantly, in M3 (worst prognosis subtype) and M2 (best prognosis subtype), the interaction between immune cells and checkpoint genes was different, which had an important effect on the prognosis. Finally, we used risk scores of immune cells and checkpoint genes to evaluate the prognosis of GBM patients and validated the results with 3 independent datasets. Disordered interactions between immune cells and checkpoint genes result in a change in the immune microenvironment and affects the prognosis of patients. We propose that a better understanding of the immune microenvironment of advanced cancers may provide new insights into immunotherapy.

| S-EPMC6558448 | biostudies-literature

Three-dimensional bioprinted glioblastoma microenvironments model cellular dependencies and immune interactions.

Project description:Brain tumors are dynamic complex ecosystems with multiple cell types. To model the brain tumor microenvironment in a reproducible and scalable system, we developed a rapid three-dimensional (3D) bioprinting method to construct clinically relevant biomimetic tissue models. In recurrent glioblastoma, macrophages/microglia prominently contribute to the tumor mass. To parse the function of macrophages in 3D, we compared the growth of glioblastoma stem cells (GSCs) alone or with astrocytes and neural precursor cells in a hyaluronic acid-rich hydrogel, with or without macrophage. Bioprinted constructs integrating macrophage recapitulate patient-derived transcriptional profiles predictive of patient survival, maintenance of stemness, invasion, and drug resistance. Whole-genome CRISPR screening with bioprinted complex systems identified unique molecular dependencies in GSCs, relative to sphere culture. Multicellular bioprinted models serve as a scalable and physiologic platform to interrogate drug sensitivity, cellular crosstalk, invasion, context-specific functional dependencies, as well as immunologic interactions in a species-matched neural environment.

| S-EPMC7608409 | biostudies-literature

Evaluation of Proton-Induced DNA Damage in 3D-Engineered Glioblastoma Microenvironments.

Project description:Glioblastoma (GBM) is a devastating cancer of the brain with an extremely poor prognosis. For this reason, besides clinical and preclinical studies, novel in vitro models for the assessment of cancer response to drugs and radiation are being developed. In such context, three-dimensional (3D)-engineered cellular microenvironments, compared to unrealistic two-dimensional (2D) monolayer cell culture, provide a model closer to the in vivo configuration. Concerning cancer treatment, while X-ray radiotherapy and chemotherapy remain the current standard, proton beam therapy is an appealing alternative as protons can be efficiently targeted to destroy cancer cells while sparing the surrounding healthy tissue. However, despite the treatment's compelling biological and medical rationale, little is known about the effects of protons on GBM at the cellular level. In this work, we designed novel 3D-engineered scaffolds inspired by the geometry of brain blood vessels, which cover a vital role in the colonization mechanisms of GBM cells. The architectures were fabricated by two-photon polymerization (2PP), cultured with U-251 GBM cells and integrated for the first time in the context of proton radiation experiments to assess their response to treatment. We employed Gamma H2A.X as a fluorescent biomarker to identify the DNA damage induced in the cells by proton beams. The results show a higher DNA double-strand breakage in 2D cell monolayers as compared to cells cultured in 3D. The discrepancy in terms of proton radiation response could indicate a difference in the radioresistance of the GBM cells or in the rate of repair kinetics between 2D cell monolayers and 3D cell networks. Thus, these biomimetic-engineered 3D scaffolds pave the way for the realization of a benchmark tool that can be used to routinely assess the effects of proton therapy on 3D GBM cell networks and other types of cancer cells.

| S-EPMC9100514 | biostudies-literature

LINC00680 and TTN-AS1 Stabilized by EIF4A3 Promoted Malignant Biological Behaviors of Glioblastoma Cells.

Project description:Glioblastomas are the most common and malignant intracranial tumors with a low survival rate. Dysregulation of long non-coding RNAs and RNA-binding protein causes various diseases, including cancers. However, the function of LINC00680 and TTN-AS1 in the progression of glioblastomas is still elusive. In this study, we detected that LINC00680 and TTN-AS1 were upregulated in glioblastoma cells. RNA-binding protein EIF4A3 could prolong the half-life of LINC00680 and TTN-AS1. Knockdown of EIF4A3, LINC00680, and TTN-AS1 impaired proliferation, migration, and invasion and inhibited the growth of tumor in vivo and promoted apoptosis of glioblastoma cells. miR-320b was proven to be a target of LINC00680 and TTN-AS1. They interacted with miR-320b as competing endogenous RNAs, which resulted in the reduction of binding between transcriptional factor EGR3 (early growth response 3) mRNA and miR-320b. The accumulation of EGR3 promoted expression of plakophilin (PKP)2, which could activate the epidermal growth factor receptor (EFGR) pathway, leading to the malignant biological behaviors of glioblastoma cells. In summary, LINC00680 and TTN-AS1 promoted glioblastoma cell malignant biological behaviors via the miR-320b/EGR3/PKP2 axis by being stabilized by EIF4A3, which may provide a novel strategy for glioblastoma therapy.

| S-EPMC7063483 | biostudies-literature

Emergent behaviors from a cellular automaton model for invasive tumor growth in heterogeneous microenvironments.

Project description:Understanding tumor invasion and metastasis is of crucial importance for both fundamental cancer research and clinical practice. In vitro experiments have established that the invasive growth of malignant tumors is characterized by the dendritic invasive branches composed of chains of tumor cells emanating from the primary tumor mass. The preponderance of previous tumor simulations focused on non-invasive (or proliferative) growth. The formation of the invasive cell chains and their interactions with the primary tumor mass and host microenvironment are not well understood. Here, we present a novel cellular automaton (CA) model that enables one to efficiently simulate invasive tumor growth in a heterogeneous host microenvironment. By taking into account a variety of microscopic-scale tumor-host interactions, including the short-range mechanical interactions between tumor cells and tumor stroma, degradation of the extracellular matrix by the invasive cells and oxygen/nutrient gradient driven cell motions, our CA model predicts a rich spectrum of growth dynamics and emergent behaviors of invasive tumors. Besides robustly reproducing the salient features of dendritic invasive growth, such as least-resistance paths of cells and intrabranch homotype attraction, we also predict nontrivial coupling between the growth dynamics of the primary tumor mass and the invasive cells. In addition, we show that the properties of the host microenvironment can significantly affect tumor morphology and growth dynamics, emphasizing the importance of understanding the tumor-host interaction. The capability of our CA model suggests that sophisticated in silico tools could eventually be utilized in clinical situations to predict neoplastic progression and propose individualized optimal treatment strategies.

| S-EPMC3245298 | biostudies-literature

JSI-124 suppresses invasion and angiogenesis of glioblastoma cells in vitro.

Project description:Glioblastoma multiforme (GBM) is one of the utmost malignant tumors. Excessive angiogenesis and invasiveness are the major reasons for their uncontrolled growth and resistance toward conventional strategies resulting in poor prognosis. In this study, we found that low-dose JSI-124 reduced invasiveness and tumorigenicity of GBM cells. JSI-124 effectively inhibited VEGF expression in GBM cells. In a coculture study, JSI-124 completely prevented U87MG cell-mediated capillary formation of HUVECs and the migration of HUVECs when cultured alone or cocultured with U87MG cells. Furthermore, JSI-124 inhibited VEGF-induced cell proliferation, motility, invasion and the formation of capillary-like structures in HUVECs in a dose-dependent manner. JSI-124 suppressed VEGF-induced p-VEGFR2 activity through STAT3 signaling cascade in HUVECs. Immunohistochemistry analysis showed that the expression of CD34, Ki67, p-STAT3 and p-VEGFR2 protein in xenografts was remarkably decreased. Taken together, our findings provide the first evidence that JSI-124 effectively inhibits tumor angiogenesis and invasion, which might be a viable drug in anti-angiogenesis and anti-invasion therapies.

| S-EPMC4366361 | biostudies-literature

ROCK Inhibition Facilitates In Vitro Expansion of Glioblastoma Stem-Like Cells.

Project description:Due to their stem-like characteristics and their resistance to existing chemo- and radiation therapies, there is a growing appreciation that cancer stem cells (CSCs) are the root cause behind cancer metastasis and recurrence. However, these cells represent a small subpopulation of cancer cells and are difficult to propagate in vitro. Glioblastoma is an extremely deadly form of brain cancer that is hypothesized to have a subpopulation of CSCs called glioblastoma stem cells (GSCs; also called brain tumor initiating cells, BTICs). We propose the use of selective Rho-kinase (ROCK) inhibitors, Y-27632 and fasudil, to promote GSC/BTIC-like cell survival and propagation in vitro. ROCK inhibitors have been implicated in suppressing apoptosis, and it was hypothesized that they would increase the number of GSC/BTIC-like cells grown in vitro and improve cloning efficiencies. Indeed, our data demonstrate that transient and continuous supplementation of non-toxic concentrations of Y-27632 and fasudil inhibited apoptosis, enhanced the cells' ability to form spheres, and increased stem cell marker expressing GSC/BTIC-like cell subpopulation. Our data indicated that pharmacological and genetic (siRNA) inhibitions of the ROCK pathway facilitates in vitro expansion of GSC/BTIC-like cells. Thus, ROCK pathway inhibition shows promise for future optimization of CSC culture media.

| S-EPMC4500389 | biostudies-literature

3D Bioprinted In Vitro Metastatic Models via Reconstruction of Tumor Microenvironments.

Project description:The development of 3D in vitro models capable of recapitulating native tumor microenvironments could improve the translatability of potential anticancer drugs and treatments. Here, 3D bioprinting techniques are used to build tumor constructs via precise placement of living cells, functional biomaterials, and programmable release capsules. This enables the spatiotemporal control of signaling molecular gradients, thereby dynamically modulating cellular behaviors at a local level. Vascularized tumor models are created to mimic key steps of cancer dissemination (invasion, intravasation, and angiogenesis), based on guided migration of tumor cells and endothelial cells in the context of stromal cells and growth factors. The utility of the metastatic models for drug screening is demonstrated by evaluating the anticancer efficacy of immunotoxins. These 3D vascularized tumor tissues provide a proof-of-concept platform to i) fundamentally explore the molecular mechanisms of tumor progression and metastasis, and ii) preclinically identify therapeutic agents and screen anticancer drugs.

| S-EPMC6996245 | biostudies-literature

Reprogramming of three-dimensional microenvironments for in vitro hair follicle induction.

Project description:During embryonic development, reciprocal interactions between epidermal and mesenchymal layers trigger hair follicle morphogenesis. This study revealed that microenvironmental reprogramming via control over these interactions enabled hair follicle induction in vitro. A key approach is to modulate spatial distributions of epithelial and mesenchymal cells in their spontaneous organization. The de novo hair follicles with typical morphological features emerged in aggregates of the two cell types, termed hair follicloids, and hair shafts sprouted with near 100% efficiency in vitro. The hair shaft length reached ~3 mm in culture. Typical trichogenic signaling pathways were up-regulated in hair follicloids. Owing to replication of hair follicle morphogenesis in vitro, melanosome production and transportation were also monitored in the hair bulb region. This in vitro hair follicle model might be valuable for better understanding hair follicle induction, evaluating hair growth and inhibition of hair growth by drugs, and modeling gray hairs in a well-defined environment.

| S-EPMC9586475 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data