Tailored biomaterial to mimic cell-cell interactions and enhance circulating tumour cell culture

• Applicant: Dr. Robert Wieduwild
• Subject Area: Biological and Biomimetic Chemistry ; Biomaterials ; Polymer Materials
• Term: from 2015 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 299417403

Most cells in the body are surrounded by a network of oligosaccharides and protein called the extracellular matrix (ECM). The ECM has a huge number of roles, providing strength to a tissue, as well as promoting cell survival, cell differentiation and guiding cells as cells move from one place to another. Specific components of the extracellular matrix, such as collagen or hyaluronic acid may be used therapeutically, but individually these components only provide a fraction of the properties of the full complex environment. We are addressing the challenge of synthesising systems that are simple to make yet incorporating more of the diversity and complexity of the ECM and therefore better mimicking its activities. In this work we will establish specific chemical reactions, using high affinity protein interactions engineered from nature, to modify the ECM polymer hyaluronic acid under conditions ideal for cell growth. By anchoring signalling molecules onto hyaluronic acid which cells would normally encounter in the body, we will provide a stimulus to keep alive cell types sensitive to their environment alive cells which would die quickly in isolation otherwise. In particular, keeping alive circulating tumour cells in artificial static environment such as those used to grow and study cells, is still a big challenge. Circulating tumour cells are released from the primary tumour and are present in the blood at every stage of tumour development. Finding these cells gives an important opportunity for early cancer diagnosis and so treatment is likely to be more successful. Having these cells available for tests would also allow improved selection of cancer treatment depending on the patient. Each individual's cancer has differences in drug sensitivity, which are critical to uncover for applying personalized medicine. Yet often a blood sample only gives 5 to 50 circulating tumour cells - not enough for drug testing. We will generate and incorporate in our matrix simple polymers able to mimic signals normally received by the circulating tumour cells and monitor how cancer cells respond and divide in response to these signals. In the long-term, augmented survival of circulating tumour cells will greatly increase the information that can be obtained from a single blood sample, both for understanding cancer and for rapidly identifying drug treatments that will be most effective for each individual.

• DFG Programme: Research Fellowships
• International Connection: United Kingdom
• Host: Professor Dr. Mark Howarth