Open AccessEx vivo Dynamics of Human Glioblastoma Cells in a Microvasculature‐on‐a‐Chip System Correlates with Tumor Heterogeneity and Subtypes
Author(s) -
Xiao Yang,
Kim Dongjoo,
Dura Burak,
Zhang Kerou,
Yan Runchen,
Li Huamin,
Han Edward,
Ip Joshua,
Zou Pan,
Liu Jun,
Chen Ann Tai,
Vortmeyer Alexander O.,
Zhou Jiangbing,
Fan Rong
Publication year - 2019
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.201801531
Subject(s) - biology , ex vivo , stem cell , cancer research , colocalization , in vivo , stromal cell , mesenchymal stem cell , motility , tumor progression , transcriptome , homing (biology) , pathology , microbiology and biotechnology , cancer , gene , gene expression , medicine , genetics , ecology
The perivascular niche (PVN) plays an essential role in brain tumor stem‐like cell (BTSC) fate control, tumor invasion, and therapeutic resistance. Here, a microvasculature‐on‐a‐chip system as a PVN model is used to evaluate the ex vivo dynamics of BTSCs from ten glioblastoma patients. BTSCs are found to preferentially localize in the perivascular zone, where they exhibit either the lowest motility, as in quiescent cells, or the highest motility, as in the invasive phenotype, with migration over long distance. These results indicate that PVN is a niche for BTSCs, while the microvascular tracks may serve as a path for tumor cell migration. The degree of colocalization between tumor cells and microvessels varies significantly across patients. To validate these results, single‐cell transcriptome sequencing (10 patients and 21 750 single cells in total) is performed to identify tumor cell subtypes. The colocalization coefficient is found to positively correlate with proneural (stem‐like) or mesenchymal (invasive) but not classical (proliferative) tumor cells. Furthermore, a gene signature profile including PDGFRA correlates strongly with the “homing” of tumor cells to the PVN. These findings demonstrate that the model can recapitulate in vivo tumor cell dynamics and heterogeneity, representing a new route to study patient‐specific tumor cell functions.