Long Prehensile Protrusions Can Facilitate Cancer Cell Invasion through the Basement Membrane

Area of Science:

• Oncology
• Cell Biology
• Biophysics

Background:

• Cancer metastasis involves breaching the basement membrane, a critical barrier.
• The mechanisms by which cancer cells physically traverse this barrier remain incompletely understood.

Purpose of the Study:

• To characterize the dynamic early steps of cancer cell invasion through basement membranes.
• To elucidate the cellular structures and mechanisms involved in breaching this barrier.

Main Methods:

• Utilized a 3D invasion model with cancer cell spheroids, basement membrane, and collagen matrix.
• Employed advanced microscopy to visualize dynamic cell behavior during invasion.

Main Results:

• Identified exceptionally long (~30-100 microm) cellular protrusions extending through basement membranes.
• Demonstrated that actin and microtubule cytoskeletal function drives protrusion formation.
• Showcased integrin adhesion and myosin II contractility enabling cells to pull through the membrane.
• Observed protrusions pulling surrounding collagen inward while propelling cells outward.

Conclusions:

• Long, contractile cellular protrusions are critical for breaching basement membranes.
• These protrusions facilitate the initial step of cancer cell invasion and metastasis.