Collagen-Based Tumor Spheroid Model for Investigating Tumor-Macrophage Interactions through Extracellular Matrix...

Area of Science:

• Oncology
• Immunology
• Biomaterials Science

Background:

• Macrophages are key components of the tumor microenvironment (TME), influencing cancer progression.
• While matrix metalloproteinases (MMPs) role in ECM degradation by macrophages is known, other ECM remodeling roles are less understood.

Purpose of the Study:

• To investigate the impact of peripheral blood mononuclear cell (PBMC)-derived macrophages on cancer cell-extracellular matrix (ECM) and cancer cell-macrophage interactions within the TME.
• To develop a 3D collagen-based tumor spheroid model for studying these interactions.

Main Methods:

• Development of a 3D collagen-based tumor spheroid model.
• Co-culture of cancer cells with peripheral blood mononuclear cell (PBMC)-derived macrophages.
• Phenotypic analysis of cancer cells and macrophages (M2-like phenotype).
• Assessment of ECM remodeling and cancer cell invasion.

Main Results:

• Cancer cells induced M2-like polarization in PBMC-derived macrophages.
• Tumor spheroid-conditioned macrophages (TSCMs) promoted cancer cell phenotypes with increased invasion and reduced circularity, indicating higher malignancy.
• TSCMs secreted factors that remodeled the ECM through degradation and fiber realignment.
• ECM remodeling created a tumor-supportive environment, facilitating cancer cell migration and invasion.

Conclusions:

• Macrophage-mediated ECM remodeling significantly contributes to cancer cell invasion and metastasis.
• The developed 3D model is a valuable platform for studying TME interactions and cancer progression.
• Targeting macrophage-mediated processes presents a potential therapeutic strategy for cancer treatment.