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An Orthotopic Glioblastoma Mouse Model Maintaining Brain Parenchymal Physical Constraints and Suitable for Intravital Two-photon Microscopy
Published on: April 21, 2014
Microgravity-induced alterations in the molecular and cellular characteristics of brain tumors: a systematic review
Mrinmoy Kundu1,2, Rafael Tiza Fernandes3,4, Anuj Kumar Sharma5
1Institute of Medical Sciences and SUM Hospital, Bhubaneswar, India.
Background:
Microgravity profoundly impacts various biological functions, including those crucial to tumorigenesis. Investigating the effects of microgravity on brain tumors is pivotal for understanding tumor biology and developing novel therapeutic strategies. This delineates the molecular and cellular characteristics of brain tumor cells under microgravity conditions.
Methodology:
The authors systematically reviewed the literature to identify relevant studies.
Results:
Microgravity has been shown to (i) induce morphological changes, where cultured glioma cells showed inhibited invasion through formation of multicellular aggregates, and ANGM5 glioblastoma multiforme (GBM) cell line showed 3D multicellular spheroid formation and loss of adhesion; (ii) inhibit cellular proliferation generally, as well as reduce invasion and migration in U87 GBM cells, however, cell viability remained high in A-172 GBM cells and human umbilical vein endothelial cells; (iii) increase DNA damage, evidenced by increased comet tail length and expression of phosphorylated γ-H2A.X, and activate apoptotic pathways in GBM and microglial cells; (iv) alter signaling pathways and protein expression through activation of ERK1/2 and AKT, altering the expression of GSK3β, Bax, and Bcl-2 in microglial and GBM cells, and through decreasing expression of vinculin and active Yap1 in GBM cells, and that of of Yap1 and ZO-1 in endothelial cells; and (v) increase chemosensitivity of GBM cells to cisplatin.
Conclusion:
Studies have shown that, across several rotary cell culture systems (RCCSs), random-position machines (RPMs), and 3D bioprinted GBM on-a-chip models, microgravity has consistently been proven to have profound effects on GBM cells. This further drills the potential role offered by microgravity as a promising anti-cancer agent in brain tumors, especially GBM.
Insights
Microgravity significantly alters brain tumor cells, affecting their morphology, proliferation, and DNA damage. These findings highlight microgravity
Area of Science:
- Space Biology
- Oncology
- Cellular Biology
Background:
- Microgravity impacts biological functions, including tumorigenesis.
- Understanding microgravity's effects on brain tumors is crucial for developing new therapies.
- This study explores molecular and cellular changes in brain tumor cells under microgravity.
Purpose of the Study:
- To delineate the molecular and cellular characteristics of brain tumor cells under microgravity.
- To investigate the potential of microgravity as an anti-cancer agent for brain tumors.
Main Methods:
- Systematic literature review to identify relevant studies.
- Analysis of data from rotary cell culture systems (RCCSs), random-position machines (RPMs), and 3D bioprinted glioblastoma multiforme (GBM) on-a-chip models.
Main Results:
- Microgravity induces morphological changes, spheroid formation, and loss of adhesion in GBM cells.
- It inhibits proliferation, invasion, and migration while increasing DNA damage and apoptosis in brain tumor cells.
- Microgravity alters signaling pathways (ERK1/2, AKT) and protein expression, and increases chemosensitivity to cisplatin in GBM cells.
Conclusions:
- Microgravity profoundly affects GBM cells across various experimental systems.
- Microgravity shows potential as a promising anti-cancer agent for brain tumors, particularly GBM.
