02150nas a2200385   4500000000100000008004100001260001500042653001100057653001700068653004100085653003600126653002700162100001500189700001600204700001500220700001800235700002100253700002000274700001800294700001500312700001700327700002000344700001600364700002000380700002200400700001900422700002300441700001900464245012600483856007200609300001100681490000700692520105100699022001401750       2026                            d  c2026-01-2710aPTPRZ110aglioblastoma10ahuman organoid tumor transplantation10aorganoid models of brain cancer10aTumor Microenvironment1 aWeihong Ge1 aRyan L. Kan1 aCan Yilgor1 aElisa Fazzari1 aPatricia R. Nano1 aDaria J. Azizad1 aHeer Shinglot1 aMatthew Li1 aJoyce Y. Ito1 aChristopher Tse1 aHong A. Tum1 aJessica Scholes1 aShivani Baisiwala1 aKunal S. Patel1 aDavid A. Nathanson1 aAparna Bhaduri00aHuman organoid tumor transplantation identifies functional glioblastoma-microenvironment communication mediated by PTPRZ1  uhttps://www.sciencedirect.com/science/article/pii/S2211124725016201  a1168480 v453 aGlioblastoma 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.  a2211-1247