Don’t push me around! Cancer cells and their turbulent relationship with their environment

A new study has explored the mechanical interactions that breast cancer cells have with their microenvironment. This has important implications for understanding tumor metastasis and tissue scaffolding.

Typically, animal cells are surrounded by a network of protein fibers known as the extra-cellular matrix (ECM). They can communicate with this environment through biochemical and mechanical signals. Over the last decade, it has become clear that the ECM is important in ensuring healthy tissue growth and promoting the proper functioning of cells.

Dr. Mina Bissel, a key researcher in this field, notes that “growth and malignant behavior is regulated at the level of tissue organization and that the tissue organization is dependent on the extracellular matrix and the microenvironment”.

The structure of this protein network is important for cell migration. This is when cells move around the tissue by pushing and pulling on collagen fibre strands. The nature of this interaction in cancer cells is still not properly understood.

A multi-disciplinary team from Cornell University and the University of Pennsylvania has tackled this problem. They set up a biomatrix of collagen fibres mixed with fluorescent beads in the in proximity to breast cancer cells. The tumour cells apply a mechanical force over their surrounding microenvironment and displace the beads over time. The displacement of the fluorescent markers was then used to calculate the force exerted by the cells on the collagen matrix.

Published in the Proceedings of the National Academy of Sciences, the study found that there is a positive feedback loop occurring in the interaction between the cancer cell and the collagen matrix. The force that the tumour cell applies on the micro-environment realigns the protein network and causes it to stiffen over time. This change causes the cancer cell to pull even harder, causing the collagen fibres to stiffen even more. Stiffening of the ECM causes an increase in the cell transmission distance of tumour cells which has implications in understanding tumour metastasis.

In future, the group will try to investigate the influence that important material properties of the ECM (such as plasticity and stress relaxation) have on tumour cell migration. A greater understanding of the role that the ECM plays in tumour metastasis can help in developing new and effective methods for preventing the spread of malignant tumours.

Andris Piebalgs is studying for a PhD in Chemical Engineering

Banner Image: Cancer Cells, Dr Cecil Fox

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