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Biophysics

Biophysics

3D modelling unlocks insight into cancer progression

05 Apr 2018
Increasing matrix stiffness enhances cell invasion
Increasing matrix stiffness enhances cell invasion

Medics may soon have a better understanding of how tumours grow and progress, thanks to research from an international collaboration. The study examined how the various cells that comprise tumours interact, in what is known as the tumour microenvironment (Biofabrication 10 035004).

Senior author David Mooney from Harvard University explained: “The tumour microenvironment is characterized by an intricate network of interactions between different cells and the extracellular matrix (ECM). Together, these elements contribute to the microenvironmental regulation of tumour progression and the cancer’s spread to other parts of the body.

“Our aim was to better understand how these interactions work, which will ultimately help with predicting and halting the growth and spread of cancer tumours.”

To do this, the researchers developed an in vitro 3D cellular model of a lung cancer tumour on an interpenetrating hydrogel.

This allowed them to examine how macrophages – a type of cell in the body capable of engulfing and absorbing bacteria and other small cells and particles – and the stiffness of the ECM influence epithelial-to-mesenchymal transition, a fundamental step in cancer cell metastasis.

“The ECM is not just a supportive structure. It is now recognised as an essential dynamic component, hosting multiple biochemical and mechanical signals that modulate tumour progression,” said first author Marta Alonso-Nocelo, from the Health Research Institute of Santiago de Compostela. “Our results showed that, in the absence of the macrophages, changes in ECM stiffness enhanced the spread and invasiveness of the lung cancer cells. When macrophages were present, modified tumour cell growth only occurred when the ECM was in a state of high stiffness.”

The study highlights the importance of both mechanical and soluble cues in tumour progression. It also demonstrates how the mechanical properties of the tumour microenvironment can affect tumour cell growth and epithelial-to-mesenchymal transition, as well as impacting how tumour cells regulate and are affected by macrophages.

“These results deepen our understanding of how tumours grow and spread, as well as some of the catalysts for this,” said Mooney. “More study is needed, but this is a promising step towards finding ways to slow these processes.”

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