Interfacial geometry dictates cancer cell tumorigenicity

Area of Science:

• Oncology
• Biomaterials Science
• Cell Biology

Background:

• Tumor tissue contains elusive stem-like cells linked to cancer recurrence and metastasis.
• Understanding the factors that regulate these cancer stem cells is crucial for developing new therapies.

Purpose of the Study:

• To investigate the role of geometric features at the tumor tissue perimeter in priming stem-like cancer cells.
• To explore the mechanisms by which interfacial geometry influences cancer cell phenotype and behavior.

Main Methods:

• Utilized engineered extracellular matrices to control tumor tissue geometry.
• Assessed stem-cell-like characteristics in vitro.
• Evaluated tumorigenicity in murine models for primary tumor growth and pulmonary metastases.
• Analyzed modulation of cell shape, integrin α5β1 adhesion, MAPK and STAT signaling, and pluripotency signaling.

Main Results:

• Geometric features at the tumor perimeter prime cells with a stem-cell-like phenotype.
• These primed cells exhibit cancer stem cell characteristics in vitro and enhanced tumorigenicity in vivo.
• Interfacial geometry was shown to modulate cell shape, integrin α5β1-mediated adhesion, MAPK and STAT activity, and pluripotency signaling.
• A general mechanism for cancer cell state regulation triggered by interfacial geometry was identified across several human cancer cell lines.

Conclusions:

• Interfacial geometry is a critical factor in regulating cancer stem cell phenotypes.
• Cancer can exploit physical cues, such as geometry, to orchestrate oncogenesis, similar to its co-option of soluble signaling pathways.
• These findings highlight a novel mechanism by which tumors can promote their own growth, recurrence, and metastasis.