Crossing Barriers: In Vitro Cancer Model for Studying Monocyte Migration across Endothelial Barriers.

Area of Science:

• Oncology
• Cell Biology
• Biomedical Engineering

Background:

• Monocytes are white blood cells that migrate to damaged tissues and differentiate into macrophages or dendritic cells.
• In glioblastoma, monocytes become tumor-associated macrophages (TAMs), promoting tumor progression and metastasis.
• Endothelial cell (EC) barriers critically influence monocyte migration, activation, and polarization.

Purpose of the Study:

• To investigate the role of an endothelial cell barrier in monocyte migration within a cancer model.
• To assess the utility of the IFlowPlate organ-on-a-chip device for studying transendothelial monocyte migration.
• To elucidate the impact of EC barriers on monocyte activation and cytokine secretion in the context of glioblastoma.

Main Methods:

• Utilized the IFlowPlate, a high-throughput organ-on-a-chip device with 128 tissue compartments.
• Embedded patient-derived glioblastoma spheroids in fibrin hydrogels with an EC barrier mimicking the vessel wall.
• Observed THP-1 monocyte migration in the presence of glioblastoma spheroids, interstitial flow, and an EC barrier (HUVECs).
• Measured inflammatory cytokine secretion levels.

Main Results:

• The presence of a human umbilical vein endothelial cell (HUVEC) barrier significantly slowed and reduced monocyte migration compared to controls without a barrier.
• Monocyte activation was confirmed by altered cytokine profiles: increased GM-CSF, IL-6, IL-10, IL-1β; decreased TNF-α, IL-12p40; unchanged MCP-1, IL-8.
• The EC barrier plays a crucial role in controlling monocyte migration and activation.

Conclusions:

• The IFlowPlate, incorporating a functional EC barrier, effectively models in vitro monocyte migration.
• EC barriers are vital for regulating monocyte behavior, influencing their role in cancer prognosis.
• This model provides a platform for high-throughput screening to study monocyte roles in cancer.