An engineered glioblastoma model yields macrophage-secreted drivers of invasion

Authors:
Open Access
Publisher website
Google Scholar
Abstract
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.
All Related Versions
Funding Information
  • National Science Foundation (DGE 1752814)
  • National Institutes of Health (R01CA260443,R01CA227136)
  • National Science Foundation (DGE 2146752)
  • National Institutes of Health (P30-CA008748)

This publication has 92 references indexed in Scilit: