Most patients who die from bowel cancer do so because it has spread to other organs (metastasis). Once the disease has spread, survival rates are poor, less than 10% of patients survive for 5 years. It is thus essential to improve both early detection of bowel cancer, and treatment of metastatic disease.

We will investigate tiny packages released by bowel cancer cells called vesicles. Vesicles can leave the bowel and circulate around the body, eventually arriving at other tissues. This is a way that bowel cancer creates suitable environments for a metastasis to establish.

Our research group has developed a 3D laboratory model mimicking bowel cancer cells growing within normal colon tissue, and this project will develop similar models of common metastatic sites (liver and lung). These models will be used to compare how vesicles interact with different tissues, and to understand why bowel cancer tends to metastasise there.

Using cutting-edge techniques to analyse our models and bowel cancer vesicles will enable us to assess how metastases establish. This will help development of new treatments blocking these processes, focused on advanced stage disease and metastatic sites. Finally, because vesicles circulate in patients, measuring them could allow earlier detection of metastasis.

Extracellular Vesicles: small packages with a big role in bowel cancer metastasis.

Patients with metastatic colorectal cancer (CRC) have poor survival rates, reflecting the difficulty in treating advanced disease. The events that lead to CRC metastases establishing are poorly understood; recently it has been proposed that extracellular vesicles (EVs) condition metastatic sites through organ-specific uptake.

This project will determine the molecular processes driving metastasis and the role of EVs, aiming to develop new treatment approaches for advanced disease and to support monitoring and diagnosis of metastatic CRC.

We will develop molecular signatures of metastatic progression in vitro, linked to histological and biomechanical features of tissue remodelling. Identifying key pathways linked to metastasis and important site-specific features will provide a basis for treatment approaches.

We will use molecular manipulation to assess the putative role of a key mediators of invasion identified in this profiling, including the important enzyme TG2. We will then link EV miRNA profiles to their effects, identifying potential biomarkers of metastasis.

The researchers

This project will be led by Dr Nicholas Peake, Senior Lecturer in Biomedical Sciences at Sheffield Hallam University. We are funding Sonia Guarnerio's PhD studies.