2. Academic Validation
  3. Glycoprotein NMB mediates bidirectional GSC-TAM interactions to promote tumor progression

Glycoprotein NMB mediates bidirectional GSC-TAM interactions to promote tumor progression

  • JCI Insight. 2025 Jul 8;10(13):e187684. doi: 10.1172/jci.insight.187684.
Yang Liu 1 2,  Lizhi Pang 1 2,  Fatima Khan 1 2,  Junyan Wu 2,  Fei Zhou 1 2,  Craig Horbinski 2,  Shideng Bao 1 3,  Jennifer S Yu 1 3,  Justin D Lathia 3 4,  Peiwen Chen 1 2 3
Affiliations

Affiliations

  • 1 Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
  • 2 Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
  • 3 Case Comprehensive Cancer Center, Cleveland, Ohio, USA.
  • 4 Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
PMID: 40626360 DOI: 10.1172/jci.insight.187684
Abstract

Glioblastoma (GBM) is a lethal brain tumor containing a subpopulation of GBM stem cells (GSCs) that interaction with surrounding cells, including infiltrating tumor-associated macrophages and microglia (TAMs). While GSCs and TAMs are in close proximity and likely interact to coordinate tumor growth, a limited number of mechanisms have been identified that support their communication. Here, we identified glycoprotein NMB (GPNMB) as a key factor mediating a unique bidirectional interaction between GSCs and TAMs in GBM. Specifically, GSCs educated macrophages and microglia to preferentially express GPNMB in the GBM tumor microenvironment. As a result, TAM-secreted GPNMB interacted with its receptor CD44 on GSCs to promote their glycolytic and self-renewal abilities via activating the Pyk2/RSK2 signaling axis. Disrupting GPNMB-mediated GSC-TAM interplay suppressed tumor progression and self-renewal in GBM mouse models. Our study found a protumor function of GPNMB-mediated GSC-TAM bidirectional communication and supports GPNMB as a promising therapeutic target for GBM.

Keywords

Brain cancer; Immunology; Oncology.

Figures
Products