Understanding how cancer cells grow and change could be the key to disrupting how they proliferate. Dr Griselda Awanis is using a new tracking technology to understand just this.

Growing tumour models
Lack of tumour samples for research has hindered progress in developing new drug therapies. To overcome this, our lab pioneered models where circulating tumour cells (CTCs) are isolated from patients’ readily obtainable blood samples and the CTCs are then injected into the mouse where they will grow into a tumour. We call these tumours, CTC-Derived eXplant (CDX) models, and multiple CDX models can be generated from different patients’ CTCs. Our SCLC CDX models mimic the appearance and the chemotherapy responses of their patient donors. These models are powerful tools for us to investigate the biology of SCLC and their development in different patients.Halting tumour growth
One strategy to halt tumour growth is by preventing adequate tumour blood supply. Tumour cells get oxygen and nutrients to grow by diverting the surrounding normal blood vessels into the tumour by a process called angiogenesis. However, an alternative process is called vasculogenic mimicry (VM) where, as tumours outstrip their oxygen and nutrient supply, tumour cells make their own vessels that join up with normal blood vessels. In SCLC, the presence of VM vessels have been shown to accelerate the growth of tumours and impact the survival of patients. Our lab discovered a particular type of SCLC cell, a non-neuroendocrine (non-NE) cell, undergoes VM. We have isolated the non-NE cells from the tumours and demonstrated the cells can organise themselves into hollow tube-like structures on a dish, which reflects their VM-forming capacity in tumours. However, it is still not known how VM vessels develop in the tumour and why some patients have more VM vessels. To answer this question, I will map out the types of vessels in CDX tumours by using a novel multi-coloured labelling process.Multi-coloured cells are created based on the principles of mixing of the 3 primary colours: red, green and blue. Red, green and blue LeGO vectors are used which can make cells express the three colours however as each cell will randomly express different amounts of the 3 colours this leads to each cell becoming a unique random colour. My aim is to track the coloured cells in the tumour and see what coloured cell can morph into the non-NE cells becoming VM vessels. If only one specific coloured cell can transform into non-NE cells and VM vessels, I can further investigate whether there are any unique features of these cells for them to form VM vessels in the tumour. This will help to develop any potential therapeutic targets to stop the cells from making VM vessels in the tumour and essentially ’starve’ tumours of their blood supply. This may serve as a new alternative strategy to tackle SCLC and with more than 200,000 cases of SCLC every year, and a five-year survival rate of less than 7%, it stands to have a mighty impact on cancer treatment.

Biotechnology is one of The University of Manchester’s research beacons - exemplars of interdisciplinary collaboration and cross-sector partnerships that lead to pioneering discoveries and improve the lives of people around the world. For more information, head to The University of Manchester’s Biotechnology page.