Cancer cell-monocyte co-culture spheroids recapitulate pro-tumorigenic, immunosuppressive, and drug-resistant microenvironments in brain metastatic breast cancer
Year: 2025
Type: article
Abstract: Monocyte derived macrophages (MDMs) comprise a major cellular fraction of the brain metastatic breast cancer (BMBC) tumor microenvironment (TME), however, their role in BMBC growth and response to therapeutics remains elusive. We developed heterotypic three-dimensional (3D) co-culture spheroid platform of triple negative BMBC cell line MDA-MB-231Br or BMBC patient xenograft derived cell line F2-7 and THP1 monocytes and assessed the impact of monocytes/MDMs on BMBC proliferation, immune modulation, and response to paclitaxel. BMBC cell and monocyte interactions enhanced BMBC cell proliferation and upregulated markers pertaining to M2 macrophage, immune suppression and evasion. Additionally, F2-7 and monocyte co-culture upregulated M1 macrophage and both pro- and anti-inflammatory markers. Co-culture spheroids exhibited higher resistance to paclitaxel as compared to monoculture BMBC spheroids. Our 3D co-culture platform successfully recapitulated to an extent the pro-tumorigenic, immunosuppressive, therapy resistant TME, and tumor immune heterogeneity of BMBC and could contribute towards understanding tumor immune interactions in BMBC.
Source: npj Breast Cancer
Authors: Sumiran Kumar Gurung, Kyra Berger, Shreyas S. Rao
Institution: University of Alabama
Language: English
Topic: Immune cells in cancer
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,790
OpenAlex ID: W4416985661