An engineered glioblastoma model yields-secreted drivers of invasion Journal Article
| Authors: | Akins, E. A.; Wilkins, D.; Abou-Mrad, Z.; Hopland, K.; Osorio, R. C.; Yu, K. K. H.; Aghi, M. K.; Kumar, S. |
| Article Title: | An engineered glioblastoma model yields-secreted drivers of invasion |
| Abstract: | While the accumulation of tumor-associated macrophages (TAMs) in glioblastoma (GBM) has been well documented, targeting TAMs has thus faryielded 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-beta 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. |
| Keywords: | gene; protein; brain; microenvironment; macrophages; identification; growth-factor-beta; cell-adhesion; mechanical-properties; s100a9 |
| Journal Title: | JCI Insight |
| Volume: | 10 |
| Issue: | 16 |
| ISSN: | 2379-3708 |
| Publisher: | Amer Soc Clinical Investigation Inc |
| Date Published: | 2025-08-22 |
| Start Page: | e181903 |
| Language: | English |
| ACCESSION: | WOS:001556318000001 |
| DOI: | 10.1172/jci.insight.181903 |
| PROVIDER: | wos |
| PMCID: | PMC12406725 |
| PUBMED: | 40857405 |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Source: Wos |
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