Influence of Macrophages on Vascular Invasion of Inflammatory Breast Cancer Emboli Measured Using an In Vitro...

Area of Science:

• Oncology
• Biomedical Engineering
• Cell Biology

Background:

• Inflammatory breast cancer (IBC) is an aggressive malignancy with limited therapeutic options.
• Understanding tumor microenvironment interactions, particularly with tumor-associated macrophages (TAMs), is crucial for developing targeted therapies.

Purpose of the Study:

• To develop and utilize a 3D in vitro microfluidic platform to investigate the role of TAMs in IBC progression.
• To elucidate the impact of different macrophage phenotypes (M0, M1, M2) on IBC cell behavior and the tumor microenvironment.

Main Methods:

• A 3D microfluidic platform was engineered using a collagen matrix, an endothelialized vessel, IBC cells (MDA-IBC3), and THP1-derived macrophages (M0, M1, M2).
• The platform facilitated physiologically relevant cellular interactions to study angiogenesis, vascular permeability, extracellular matrix (ECM) remodeling, and intravasation.
• Cytokine analysis (IL-8, MMP9) was performed to assess the inflammatory response.

Main Results:

• TAMs significantly increased blood vessel sprouting and endothelial permeability, irrespective of macrophage phenotype.
• Platforms with M1 or M2 macrophages showed increased ECM porosity compared to M0 or IBC cells alone.
• IL-8 and MMP9 levels were selectively elevated in the presence of macrophages.
• Tumor cell intravasation into vessels occurred only in the presence of MDA-IBC3 and M0 macrophages.

Conclusions:

• TAMs play a significant role in promoting IBC angiogenesis and vascular permeability.
• Macrophage phenotype influences ECM remodeling and the potential for tumor cell dissemination.
• The 3D microfluidic platform provides a valuable model for studying IBC and identifying potential therapeutic targets.