Soft matrix is a natural stimulator for cellular invasiveness

Area of Science:

• Cell Biology
• Biophysics
• Biochemistry

Background:

• Cellular invasion is typically viewed as a stimulated process regulated by external factors.
• The role of extracellular matrix (ECM) stiffness in regulating cell behavior, particularly invasion, requires further investigation.

Purpose of the Study:

• To investigate the direct impact of ECM stiffness on cellular invasion mechanisms.
• To determine if ECM stiffness alone can induce invasive phenotypes.

Main Methods:

• Utilized varying ECM stiffness substrates to culture primary human fibroblasts, cancer cells, and fibrosarcoma cells.
• Assessed cell-to-cell adherens junction formation, matrix metalloproteinase (MMP) secretion and activity, and invadosome-like protrusion (ILP) formation.
• Employed a three-dimensional directional invasion assay in soft matrix.

Main Results:

• Soft ECM (low stiffness) inhibited stable cell-to-cell adherens junction formation.
• Soft ECM induced upregulation of MMP secretion and activity, and promoted ILP formation.
• Primary fibroblasts formed ILPs in a narrow stiffness range (0.1-0.4 kPa) dependent on Src family kinases.
• Malignant cancer and fibrosarcoma cells exhibited spontaneous ILP formation across a wider stiffness range, with increased prominence at lower stiffness.

Conclusions:

• ECM stiffness is a critical regulator of cellular invasiveness.
• Soft ECM acts as a natural stimulator for cellular invasion by promoting MMP activity and ILP formation.
• Tumor cells display altered responses to ECM stiffness, suggesting a role in their enhanced invasiveness.