Hannah Mackay

2016 AFPGR Participant

 

Cannibalistic Cancer Cells: eat or be eaten
About Hannah

Hannah has just started the third year of her PhD project under the supervision of Dr. Patricia A J Muller and Dr. John Le Quesne. Hannah is based at the MRC Toxicology Unit near the University of Leicester.

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My Research Project

My research focuses on a finding that was first discovered by pathologists over 100 years ago, but only now being investigated for its potential biological importance. A ‘cell-in-cell’ structure exists when one viable cell is enclosed within another viable cell. This appears to be a trait that only cancer cells have and has been observed in a number of cancer types including skin, urothelial, endometrial, breast, blood, pancreatic and carcinoma of the lung.

There is much controversy as to the mechanism, prevalence and implications of these structures. It has been described both as a process of engulfment and invasion. It has been linked to the presence and severity of metastasis but also as a mechanism of cell death that prevents metastasis. Its prevalence throughout so many tumour types coupled with large gaps in knowledge means this field does need more focus. There is a need to increase our understanding of how these structures arise and what it means when they do.

Research Findings

The collaboration between my supervisors provides me with the scope to explore cell-in-cell structures from both a clinical and biological perspective.

Clinically, I have access to a large collection of archival lung adenocarcinoma patient samples. From this, I have quantified cell-in-cell numbers in 206 cases to date, of which 15-20% have consistent occurrence of the structures. Furthermore, prevalence is correlated to key histological grading features, survival rates and metastatic potential. This indicates, in lung adenocarcinoma, cell-in-cell activity is associated with a worse prognosis for the patient. I am now expanding case numbers and using tumour microarrays to investigate genetic and/ or molecular biomarkers for cell-in-cell.

In the laboratory, I use fluorescent proteins (red and green) to label cancer cells. This allows visualisation and measurement of the formation and subsequent outcome of cell-in-cell structures. Time-lapse imaging has shown they are formed by a phagocytosis like engulfment mechanism, with a number of different outcomes. Manipulating the experimental set up of co cultured red and green allows the environment, cell type and genetic differences to all be controlled and therefore investigated. This will give insight into the mechanism, driving factors and more importantly significance of these structures. To date, links have been made with certain extracellular matrix components, a key tumour suppressor gene and also receptors previously linked to phagocytosis.

 

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