TY - JOUR
KW - PTPRZ1
KW - glioblastoma
KW - human organoid tumor transplantation
KW - organoid models of brain cancer
KW - Tumor Microenvironment
AU - Weihong Ge
AU - Ryan L. Kan
AU - Can Yilgor
AU - Elisa Fazzari
AU - Patricia R. Nano
AU - Daria J. Azizad
AU - Heer Shinglot
AU - Matthew Li
AU - Joyce Y. Ito
AU - Christopher Tse
AU - Hong A. Tum
AU - Jessica Scholes
AU - Shivani Baisiwala
AU - Kunal S. Patel
AU - David A. Nathanson
AU - Aparna Bhaduri
AB - Glioblastoma is the most aggressive and deadly form of brain cancer. Here, we leverage our human organoid tumor transplantation (HOTT) co-culture system to explore how extrinsic cues modulate glioblastoma cell types and behavior. HOTT recapitulates core features of major patient tumor cell types and key aspects of neural cell-enriched tumor microenvironment (nTME) gene programs. Our exploration of patient TME interactions preserved in HOTT highlights four receptor-ligand interactions of interest. We knock down all four of these genes in the HOTT microenvironment. We observe that knocking down nTME PTPRZ1, a receptor tyrosine phosphatase implicated in cancer cell migration, results in an increased fraction of mesenchymal cells, enrichment of epithelial-to-mesenchymal gene programs, and an elevated tumor microtube length in co-cultured primary patient tumors. This phenotype is not mediated by PTPRZ1’s catalytic activity, suggesting a mechanism of tumor cell fate driven by nTME PTPRZ1, highlighting the strengths of the HOTT system.
BT - Cell Reports
DA - 2026-01-27
DO - 10.1016/j.celrep.2025.116848
IS - 1
N2 - Glioblastoma is the most aggressive and deadly form of brain cancer. Here, we leverage our human organoid tumor transplantation (HOTT) co-culture system to explore how extrinsic cues modulate glioblastoma cell types and behavior. HOTT recapitulates core features of major patient tumor cell types and key aspects of neural cell-enriched tumor microenvironment (nTME) gene programs. Our exploration of patient TME interactions preserved in HOTT highlights four receptor-ligand interactions of interest. We knock down all four of these genes in the HOTT microenvironment. We observe that knocking down nTME PTPRZ1, a receptor tyrosine phosphatase implicated in cancer cell migration, results in an increased fraction of mesenchymal cells, enrichment of epithelial-to-mesenchymal gene programs, and an elevated tumor microtube length in co-cultured primary patient tumors. This phenotype is not mediated by PTPRZ1’s catalytic activity, suggesting a mechanism of tumor cell fate driven by nTME PTPRZ1, highlighting the strengths of the HOTT system.
PY - 2026
EP - 116848
T2 - Cell Reports
TI - Human organoid tumor transplantation identifies functional glioblastoma-microenvironment communication mediated by PTPRZ1
UR - https://www.sciencedirect.com/science/article/pii/S2211124725016201
VL - 45
Y2 - 2026-01-28
SN - 2211-1247
ER -