Rana’s Undergraduate Summer Bursary in Tumour Growth
Rana Haidari, a Biomedicine student, undertook a Big C funded 8-week undergraduate summer project in Dr Derek Warren‘s lab group based in the Biomedical Research Centre (BMRC), UEA. Under the supervision of Dr Robert Johnson.
What happens during tumour growth?
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 (blood vessel formation). 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.
In the context of cancer, the question remains, does increased tissue stiffness aid a tumour’s recruitment of a blood supply?
Understanding this mechanism can allow development of therapies that can block this process, preventing tumour growth/metastasis.
Does tissue stiffness cause an angiogenic response in endothelial cells?
Rana looked 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. She used polyacrylamide hydrogels, to mimic the physiological and pathological stiffness of many solid tumours.
She also investigated the effect of an increase in stiffness, which occurs as cancers grow, on endothelial cells. She found that there was an increase in the ability of endothelial cells to grow, replicate and move, all processes a tumour requires them to undergo, in order to recruit its own blood supply.
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.
During her studentship, she found 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!
In a nutshell, these findings show that anti-angiogenic therapies that work for a certain type of cancer, may not work for others and further research is needed in this field.
Personal Experience
Rana recounts that ‘this project gave me a real insight into what a research lab entails‘ as she aims to embark medical research in the future after her undergraduate degree.
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