Tumor-induced remote ECM network orientation steers angiogenesis

Area of Science:

• Biophysics
• Cancer Biology
• Biomaterials

Background:

• Tumor angiogenesis is crucial for tumor growth and metastasis.
• The mechanical properties of the tumor microenvironment play a significant role in cancer progression.
• Understanding the interplay between tumor cells and the extracellular matrix (ECM) is vital for developing new therapeutic strategies.

Purpose of the Study:

• To investigate the mechanical aspects of tumor angiogenesis.
• To explore how tumor cells influence the surrounding extracellular matrix (ECM).
• To determine the role of ECM remodeling in guiding endothelial cell migration during angiogenesis.

Main Methods:

• Automated sequential microprinting of tumor and endothelial cells within ECM scaffolds.
• Quantitative reflection microscopy to analyze collagen fiber orientation.
• Laser ablation experiments to assess the requirement of physical connections for cell sensing.

Main Results:

• Tumor spheroids induce radial orientation of collagen fibers up to five times their radius.
• Remote collagen orientation correlates with tumor cell migration.
• Endothelial cells migrate directionally towards tumor spheroids within the oriented collagen network.
• Mechanical sensing by endothelial cells requires an intact physical connection to the oriented ECM.

Conclusions:

• Tumor cells can remotely manipulate the ECM by reorienting collagen fibers.
• This ECM remodeling is essential for guiding endothelial cell migration and angiogenesis.
• Physical manipulation of the ECM, alongside soluble factors, contributes to steering tumor angiogenesis.