Rana’s Undergraduate Tumour Growth Research

My name is Rana Haidari, and I am going into my 3rd year studying Biomedicine at the University of East Anglia. I recently completed my 8 weeks undergraduate tumour growth research project within the lab of Dr Derek Warren, based within the Biomedical Research Centre (BMRC), UEA, under the supervision of Dr Robert Johnson. My aim is to do medical research in the future and this project gave me a real insight into what a research lab entails.

Tumours

As tumours grow, they change their surrounding environment to suit the needs of the tumour – this includes recruiting their own blood supply via the process of angiogenesis. One change that has been observed is the stiffness of the tissue surrounding the tumour increases. Tissue stiffness has recently been shown to regulate cell behaviour. We want to know if in the context of cancer, of increased tissue stiffness can aid a tumours recruitment of a blood supply, with the aim being if we understand how tumours recruit a blood supply, we can subsequently develop therapies that block this process, starving a tumour and prevent its growth / metastasis.

Endothelial Cells

I was looking at how the behaviour of endothelial cells, the cell type that make up our blood vessels, changes based on the stiffness of the surface they are grown on. I was also looking to see if an increase in stiffness, which occurs as cancers grow, leads to an increase in the ability of endothelial cells to grow, replicate and move, processes a tumour requires them to undergo, in order to recruit its own blood supply.

Does matrix stiffness activate a pro-angiogenic switch within endothelial cells?

To investigate this, we grew endothelial cells on polyacrylamide hydrogels, substrates whose stiffness can be tuned to mimic the physiological and pathological stiffness of many solid tumours. As we increased the stiffness of these hydrogels, we noticed that endothall proliferation (growth), migration speed and spreading all increased, indicating that endothelial cells were undergoing an angiogenic response to matrix stiffness.

Anti-angiogenic therapies

Anti-angiogenic therapies have long been hypothesised to be a potential cancer treatment. Despite promising pre-clinical findings, anti-angiogenic therapies typically fail during Phase I or II clinical trials, showing little to no benefit to the patient. When studying the behaviour of endothelial cells, those which comprise our blood vessels, the vast majority of studies have been performed on glass or plastic, materials whose stiffness is 1000x greater than the tissues in which solid tumours typically form.

Findings

Given that the extra-cellular environment surrounding tumour cells stiffens as the tumour grows, investigating the angiogenic behaviour of endothelial cells on physiological and pathologically relevant substrate stiffnesses may provide novel insight to how tumour angiogenesis occurs. Research from this studentship has revealed that the angiogenic behaviour of endothelial cells is regulated by substrate stiffness. Not only that, but that endothelial cells from specific tissues may be adapted to the stiffness of their host tissue. This means that anti-angiogenic therapies that work for kind of cancer may not work for others.