Influence of porosity on cancer cells
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Influence of Porosity on Cancer Cells
Introduction to Porosity and Cancer Cell Behavior
The extracellular matrix (ECM) plays a crucial role in cancer cell behavior, influencing processes such as invasion, proliferation, and metastasis. Among the various physical properties of the ECM, porosity is a significant factor that affects how cancer cells interact with their environment. This article synthesizes recent research findings on the influence of ECM porosity on cancer cells.
Porosity and Cancer Cell Invasion
Elasticity and Porosity-Tunable Matrices
Research has shown that the porosity of the ECM can significantly impact cancer cell invasion. A study developed elasticity/porosity-tunable electrospun fibrous gel matrices to independently modulate these properties. It was found that highly malignant MDA-MB-231 cells exhibited the highest degree of matrix metalloproteinase (MMP)-independent invasion in matrices with a Young’s modulus of 20 kPa and low interfiber bonding, indicating low porosity. In contrast, non-tumorigenic MCF-10A cells did not show invasive behavior under the same conditions.
Macroporosity and Cancer Cell Proliferation
Another study focused on the effects of macroporosity and stiffness of ECM simulations on ovarian cancer cells. Increased macroporosity and stiffness were found to enhance the proliferation and aggregation of ovarian SKOV-3 cancer cells. This suggests that higher porosity in the ECM can facilitate cancer cell proliferation and aggregation, contributing to tumor growth and metastasis .
Porosity and Tumor Microenvironment
Stiffness and Porosity in Tumor Growth
A computational model investigating the role of ECM stiffness and porosity in tumor growth revealed that higher matrix porosities favor the growth and dissemination of tumor cells. Specifically, a modest increase in the porosity parameter from 0.7 to 0.9 was associated with a 300% increase in tumor mass. This highlights the critical role of ECM porosity in regulating tumor expansion and spreading.
Physical Cues and Cancer Cell Behavior
The physical cues of the tumor microenvironment, including porosity, significantly contribute to cancer progression. Changes in ECM porosity can affect cancer cell stiffness, actin cytoskeleton organization, gene and protein expressions, and migration. These mechanical signals are transferred to downstream signaling pathways, ultimately influencing cellular behaviors and responses to treatments.
Porosity and Cancer Cell Morphology
Collagen Networks and Cell Invasion
In studies using 3D collagen networks, it was demonstrated that pore size and fibril diameter distinctly regulate cancer cell morphology and invasion. While pore size was a major determinant of matrix elasticity, fibril diameter primarily regulated cell morphology, cluster formation, and invasion. This indicates that the structural properties of the ECM at the microscale, such as porosity, play a crucial role in determining cancer cell behavior.
Conclusion
The porosity of the ECM is a critical factor influencing cancer cell invasion, proliferation, and overall behavior. Higher porosity generally facilitates cancer cell proliferation and invasion, contributing to tumor growth and metastasis. Understanding the role of ECM porosity can provide valuable insights into cancer progression and potential therapeutic targets. Future research should continue to explore the complex interactions between ECM properties and cancer cell dynamics to develop more effective cancer treatments.
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