Glioblastoma (GBM) is a highly invasive primary brain tumor that, although rarely metastasizing outside the brain, frequently infiltrates surrounding brain tissue. This infiltrative growth may exploit the brain’s metabolic support system, which involves various brain-resident cells providing essential nutrients and maintaining energy balance. In this study, we investigated the metabolic dependencies of infiltrative GBM cells by combining spatially resolved transcriptomic profiling with advanced computational methods in xenografted GBM models. Our findings reveal that GBM cells upregulate creatine kinase brain type (CKB) at the leading edge to adapt to local energy deprivation. CKB facilitates the conversion of creatine to phosphocreatine, utilizing ATP supplied by astrocytes to support tumor cell survival and invasion. Targeting CKB with cyclocreatine significantly reduced tumor size and restricted infiltrative growth in vivo, indicating that GBM cells utilize CKB to harness extracellular ATP via the creatine pathway. These findings suggest that targeting CKB in GBM may offer a novel therapeutic strategy to combat infiltrative growth in this aggressive cancer.
from sddb import Catalog
cohort = Catalog().collection("geo-gse283959")
cohort.members # the 4 datasets as a table
print(cohort.licenses()) # check the terms before you download
sdatas = cohort.to_dict() # {uid: SpatialData}, cached locally
# or keep the .zarr files in a folder of your choice:
# sdatas = cohort.to_dict(dest="data/")Needs pip install lamindb and network access to the Lamin database, which is limited during the alpha. If it fails, use the Client tab.
import lamindb as ln
db = ln.DB("scverse/spatialdata-db")
coll = db.Collection.get(key="geo-gse283959")
coll.ordered_artifacts.to_dataframe() # the 4 members, ordered
# download every member .zarr to the local cache:
paths = [a.cache() for a in coll.ordered_artifacts.all()]# sddb client: download every member .zarr into data/
sddb-cli download --collection geo-gse283959 --dest data/Licenses: 4 NCBI GEO policy
@article{Yang_2025,
title = {Glioblastoma exploits ATP from leading-edge astrocytes to fuel its infiltrative growth revealed by spatially resolved chimeric analysis},
volume = {11},
ISSN = {2375-2548},
url = {http://dx.doi.org/10.1126/sciadv.adv5673},
DOI = {10.1126/sciadv.adv5673},
number = {39},
journal = {Science Advances},
publisher = {American Association for the Advancement of Science (AAAS)},
author = {Yang, Gaoxia and Niu, Xiaodong and Gan, Jieying and Yu, Tianping and Li, Menghan and Xiao, Peng and Zhang, Rui and He, Ping and Yang, Yuan and Cui, Yi and Huang, Xiaoyi and Wang, Yuan and Mao, Qing and Zhou, Ran},
year = {2025},
month = Sept
}