This project explores the role of a particular cell type – the pericyte – that is present in the immediate cellular environment of cancers, in promoting tumour growth. The results will lead to the identification of methods to better diagnose those patients at greater risk of recurrent cancer.
It is well accepted that the cells found in the local microenvironment of cancer cells play a significant role in tumour development and growth. A number of cell types found adjacent to solid tumours have been implicated including connective tissue stromal cells, blood derived immune cells, and blood vessel lining endothelial cells.
Although, fibroblasts comprise the majority of stromal cells within the tumour environment, a subset of these are consistently associated with neoplastic lesions and have been named cancer-associated fibroblasts. Correlative studies from our laboratory suggest that pericytes found in the environment of all epithelial tissues may be recruited to promote tumour growth acting as the elusive cancer-associated fibroblasts. This project seeks to provide experimental proof that pericytes accelerate the aggressive growth and spread of tumours.
Pericytes are known to control new blood vessel formation, which is critical to tumour expansion. However, we propose that pericytes have an unrecognized role in increasing tumour growth directly by the secretion of growth factors and proteins, and further that this can be proven by co-inoculation of tumour cells with pericytes.
We have made some tools that will assist us in strengthening our initial visual observations of tumour acceleration e.g. fluorescently tagged tumour cells (green) and pericytes (red), so that the tumour sizes can be measured by a machine and statistically significant differences in tumour growth determined.
Our study will provide support for the idea that pericytes, present throughout the body surrounding blood vessels, may be hijacked into promoting tumour growth and represent the much sought after cancer associated fibroblasts.
This idea has profound implications for understanding the development of the majority of cancers throughout the body e.g. bowel, breast, head and neck, ovary, prostate etc and may provide a basis for defining new markers that will be vital in the diagnosis (and potentially prognosis) of those patients at high risk of cancer recurrence and mortality.