Protrusion force and cell-cell adhesion-induced polarity alignment govern collective migration modes

Area of Science:

• Cell Biology
• Biophysics
• Cancer Research

Background:

• Collective cell migration enhances cancer invasion and metastasis.
• Mechanisms regulating tumor migration plasticity and collective behavior are poorly understood.
• Hypoxia significantly influences the tumor microenvironment and cancer cell behavior.

Purpose of the Study:

• To provide a mechanistic framework for understanding different modes of collective cell migration.
• To investigate the role of hypoxia-induced secretome in regulating tumor migration.
• To elucidate the interplay between cellular protrusion force and cell-cell adhesion in microtumor migration.

Main Methods:

• Development of a minimal multi-scale microtumor model (MSMM).
• Utilizing three-dimensional microtumors with defined microenvironments.
• Combining experimental and computational modeling approaches.

Main Results:

• Distinct collective migration modes (radial and directional) were identified based on protrusion force and cell-cell adhesion.
• Sufficient cellular protrusion force is essential for both radial and directional migration.
• Strong cell-cell adhesion promotes cell polarity alignment, leading to directional migration.

Conclusions:

• The study provides fundamental insights into collective migration mechanisms in response to microenvironmental stimuli like hypoxia.
• Cellular protrusion force and cell-cell adhesion are key regulators of collective migration modes.
• Understanding these mechanisms can inform strategies to target cancer invasion and metastasis.