According to Cancer Research UK, Breast Cancer in the third commonest type of cancer diagnosed and accounts for 15% of all female cancer deaths. A clear understanding of the biology behind this malignancy is urgently needed. With that in mind, researchers at the University of California San Francisco have unravelled the specific invasive properties of breast cancer tumours.
Acerbi et al. investigated the link between breast cancer tissue and the stiffness of the tissue scaffold, the extracellular matrix (ECM). In non-cancerous tissues, the ECM is integral for the maintenance of tissue structure and is a regulator of the dynamic communication between cells. Characteristically, the ECM is collagen-rich yet can take many forms depending on the need of the tissue because of its responsive nature. This active role of the ECM unfortunately presents the opportunity for deleterious remodelling. The researchers found that hallmarks of the tumour transformation include deposition of excessive collagen, elevated mechanosignalling and an association with a stiffened ECM at the invasive front of the tumour.
Compared to normal breast tissue, the collagen was progressively assembled into thicker fibres and linearised, causing stiffening of the ECM. Macrophages sent by the immune system release soluble factors that assist with the remodelling. The researchers correlated the influx of immune cells with the increase in SMAD signalling, a cascade which changes the gene expression of the tissue and is likely to be part of the molecular pathway behind the extra collagen production.
The core tissue of the tumour was less stiff than the invasive edge
The researchers identified that tumours caused by different breast cancer-associated mutations can have diverse ECM compositions, and even different regions of the same tumour can be biochemically distinct. This has important implications for the testing and imaging of breast cancer tumours and provides convincing evidence that the ECM is more complex in cancer pathology than previously thought.
You can read the full paper for free* using the link below:
Human breast cancer invasion and aggression correlates with ECM stiffening and immune cell infiltration
I. Acerbi, L. Cassereau, I. Dean, Q. Shi, A. Au, C. Park, Y. Y. Chen, J. Liphardt, E. S. Hwang and V. M. Weaver
Integr. Biol., 2015, Advance Article
DOI: 10.1039/C5IB00040H, Paper
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Rebecca Muir is a research assistant in the Medical Sciences Division of Oxford University. Her research interests include cell biology, gender studies, philosophy of science, and mitochondrial disease. Rebecca was shortlisted for the Chemistry World’s Science Communication Competition 2015. She tweets at @rebeccalydiam and her personal website can be found on rebeccamuir.co.uk.
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