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September 10, 2025JCI Insight5 citationsOpen Access

An engineered glioblastoma model yields macrophage-secreted drivers of invasion

EAErin AkinsBioengineering Center DWDana E. WilkinsUniversity of California, San Francisco ZAZaki Abou-MradMemorial Sloan Kettering Cancer Center

Puntos clave

Macrophages promote aggressive behaviors in glioblastoma stem cells, amplifying tumor invasion.
Key findings include the identification of TAM-secreted proteins, including TGF-β, influencing invasiveness.
Utilizing a 3D hydrogel-based model facilitated the exploration of TAM and cancer cell interactions.
This work may guide the development of therapies targeting tumor-associated macrophages in glioblastoma.

Resumen

While the accumulation of tumor-associated macrophages (TAMs) in glioblastoma (GBM) has been well documented, targeting TAMs has thus far yielded limited clinical success in slowing GBM progression due, in part, to an incomplete understanding of TAM function. Using an engineered 3D hydrogel-based model of the brain tumor microenvironment (TME), we show that M2-polarized macrophages stimulate transcriptional and phenotypic changes in GBM stem cells (GSCs) closely associated with the highly aggressive and invasive mesenchymal subtype. By combining proteomics with GBM patient single-cell transcriptomics, we identify multiple TAM-secreted proteins with putative proinvasive functions and validate TGF-β induced (TGFBI, also known as BIGH3) as a targetable TAM-secreted tumorigenic factor. Our work highlights the utility of coupling multiomics analyses with engineered TME models to investigate TAM-cancer cell crosstalk and offers insights into TAM function to guide TAM-targeting therapies.

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