Investigating the Interactions of Glioma Stem Cells in the Perivascular Niche at Single-Cell Resolution using a Microfluidic Tumor Microenvironment Model.
Adv Sci (Weinh)
; 9(21): e2201436, 2022 07.
Article
in En
| MEDLINE
| ID: mdl-35619544
ABSTRACT
The perivascular niche (PVN) is a glioblastoma tumor microenvironment (TME) that serves as a safe haven for glioma stem cells (GSCs), and acts as a reservoir that inevitably leads to tumor recurrence. Understanding cellular interactions in the PVN that drive GSC treatment resistance and stemness is crucial to develop lasting therapies for glioblastoma. The limitations of in vivo models and in vitro assays have led to critical knowledge gaps regarding the influence of various cell types in the PVN on GSCs behavior. This study developed an organotypic triculture microfluidic model as a means to recapitulate the PVN and study its impact on GSCs. This triculture platform, comprised of endothelial cells (ECs), astrocytes, and GSCs, is used to investigate GSC invasion, proliferation and stemness. Both ECs and astrocytes significantly increased invasiveness of GSCs. This study futher identified 15 ligand-receptor pairs using single-cell RNAseq with putative chemotactic mechanisms of GSCs, where the receptor is up-regulated in GSCs and the diffusible ligand is expressed in either astrocytes or ECs. Notably, the ligand-receptor pair SAA1-FPR1 is demonstrated to be involved in chemotactic invasion of GSCs toward PVN. The novel triculture platform presented herein can be used for therapeutic development and discovery of molecular mechanisms driving GSC biology.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain Neoplasms
/
Glioblastoma
/
Glioma
Limits:
Humans
Language:
En
Journal:
Adv Sci (Weinh)
Year:
2022
Document type:
Article
Affiliation country:
United States
Country of publication:
ALEMANHA
/
ALEMANIA
/
DE
/
DEUSTCHLAND
/
GERMANY