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Updated: Jun 7, 2026

Studying the Effects of Tumor-Secreted Paracrine Ligands on Macrophage Activation using Co-Culture with Permeable Membrane Supports
Published on: November 28, 2019
Tumor-Associated Macrophages Suppress HNSCC Motility and Reveal BOP1 as a Prognostic Driver
Xingyu Mu1, Guile Zhao1, Yufei Hua1
1State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases.
Abstract:
This study investigates the complex role of tumor-associated macrophages (TAMs) in the aggressive head and neck squamous cell carcinoma (HNSCC) microenvironment. Contrary to the typical protumorigenic role, functional coculture assays revealed that TAMs significantly suppressed HNSCC cell migration and invasion without affecting proliferation or apoptosis, an effect accompanied by the inhibition of epithelial-mesenchymal transition (EMT). Transcriptomic profiling identified block of proliferation 1 (BOP1) as a key gene downregulated following TAM coculture. Subsequent loss-of-function studies confirmed that silencing BOP1 alone recapitulated the suppressive effects of TAMs on cancer cell motility. Analysis of multiple independent clinical cohorts demonstrated that high BOP1 expression is significantly correlated with advanced tumor stage and worse overall survival in HNSCC patients. Importantly, elevated BOP1 levels were also associated with a reduced abundance of CD8+ T cells within the tumor microenvironment. These findings collectively unveil a tumor-restraining role for TAMs through motility and EMT inhibition, and identify BOP1 as a critical oncogenic driver that promotes HNSCC progression and is linked to impaired antitumor immunity, highlighting its dual potential as a prognostic biomarker and therapeutic target.
Insights
Tumor-associated macrophages surprisingly inhibit head and neck cancer cell movement by downregulating BOP1. High BOP1 expression predicts advanced cancer and poor immunity, suggesting it as a therapeutic target.
Area of Science:
- Oncology
- Immunology
- Cancer Biology
Background:
- Head and neck squamous cell carcinoma (HNSCC) is aggressive.
- Tumor-associated macrophages (TAMs) often promote cancer but their role in HNSCC is complex.
Purpose of the Study:
- To investigate the role of TAMs in HNSCC.
- To identify molecular mechanisms underlying TAM function in HNSCC.
- To evaluate BOP1 as a prognostic biomarker and therapeutic target in HNSCC.
Main Methods:
- Coculture assays of TAMs and HNSCC cells.
- Transcriptomic profiling to identify key genes.
- Loss-of-function studies (gene silencing).
- Analysis of clinical HNSCC patient cohorts.
Main Results:
- TAMs suppressed HNSCC cell migration, invasion, and epithelial-mesenchymal transition (EMT).
- Block of proliferation 1 (BOP1) was downregulated by TAMs and its silencing mimicked TAM effects.
- High BOP1 expression correlated with advanced HNSCC stage, poor survival, and reduced CD8+ T cells.
Conclusions:
- TAMs exhibit a tumor-restraining role in HNSCC by inhibiting motility and EMT.
- BOP1 is an oncogenic driver promoting HNSCC progression and immune evasion.
- BOP1 is a potential prognostic biomarker and therapeutic target for HNSCC.
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