@article{7001,
  keywords = {PTPRZ1, glioblastoma, human organoid tumor transplantation, organoid models of brain cancer, Tumor Microenvironment},
  author = {Weihong Ge and Ryan L. Kan and Can Yilgor and Elisa Fazzari and Patricia R. Nano and Daria J. Azizad and Heer Shinglot and Matthew Li and Joyce Y. Ito and Christopher Tse and Hong A. Tum and Jessica Scholes and Shivani Baisiwala and Kunal S. Patel and David A. Nathanson and Aparna Bhaduri},
  title = {Human organoid tumor transplantation identifies functional glioblastoma-microenvironment communication mediated by PTPRZ1},
  abstract = {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.},
  year = {2026},
  journal = {Cell Reports},
  volume = {45},
  pages = {116848},
  month = {2026-01-27},
  issn = {2211-1247},
  url = {https://www.sciencedirect.com/science/article/pii/S2211124725016201},
  doi = {10.1016/j.celrep.2025.116848},
}