Human organoid tumor transplantation identifies functional glioblastoma-microenvironment communication mediated by PTPRZ1

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…

• AC
  American Cancer Society
• AP
  Alfred P. Sloan Foundation
• VF
  V Foundation for Cancer Research
• SF
  Sontag Foundation
• RH
  Rose Hills Foundation
• SA
  Swim Across America
• UK
  Uncle Kory Foundation
• NC
  National Cancer Institute
• JC
  Jonsson Comprehensive Cancer Center
• EA
  Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles