RT Journal Article
SR Electronic
T1 Identification of Cancer-Associated Fibroblasts in Glioblastoma and Defining Their Pro-tumoral Effects
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.05.08.443250
DO 10.1101/2021.05.08.443250
A1 Saket Jain
A1 Jonathan W. Rick
A1 Rushikesh Joshi
A1 Angad Beniwal
A1 Jordan Spatz
A1 Alexander Chih-Chieh Chang
A1 Alan T. Nguyen
A1 Sweta Sudhir
A1 Ankush Chandra
A1 Alex Haddad
A1 Harsh Wadhwa
A1 Sumedh S. Shah
A1 Serah Choi
A1 Josie L. Hayes
A1 Lin Wang
A1 Garima Yagnik
A1 Joseph F. Costello
A1 Aaron Diaz
A1 Manish K. Aghi
YR 2021
UL http://biorxiv.org/content/early/2021/05/10/2021.05.08.443250.abstract
AB Despite their identification in some cancers, pro-tumoral cancer-associated fibroblasts (CAFs) were presumed absent in glioblastoma given the lack of brain fibroblasts. Serial trypsinization of primary glioblastoma cultures yielded cells with CAF morphology, CAF transcriptomic profile, and mesenchymal lineage in single-cell RNA-seq. Glioblastoma CAFs were attracted to glioblastoma stem cells (GSCs) and CAFs enriched GSCs. We created a resource of inferred crosstalk by mapping expression of receptors to their cognate ligands, identifying PDGF-β and TGF-β as mediators of GSC effects on CAFs, and osteopontin and hepatocyte growth factor as mediators of CAF-induced GSC enrichment. Glioblastoma CAFs also induced M2 macrophage polarization by producing the EDA fibronectin variant. Glioblastoma CAFs were enriched in the subventricular zone which houses neural stem cells that produce GSCs. Including CAFs in GSC-derived xenografts induced in vivo growth. These findings are among the first to identify glioblastoma CAFs and their GSC interactions, making them an intriguing target.Competing Interest StatementThe authors have declared no competing interest.