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Ensnaring tumours in their own web

Erik Danen is looking at how to inhibit tumours that do not respond well to medicine – and he is making some headway. The Professor of Cancer Drug Target Discovery studies the interaction between tumour cells and their surroundings. Inaugural lecture on Friday 10 May.

The cells in our bodies are caught in a web in which they receive copious instructions from growth factors, neighbouring cells and the medium in which they are found: the extracellular matrix. This is hard in bone and soft in lung tissue, for instance, and cells can ‘sense’ this. The instructions from outside determine the identity and behaviour of cells. However, this goes awry with diseases such as cancer, and tumour cells take less notice of their environment and start doing their own thing instead. With his research into the interaction between cells and their environment, Erik Danen, Professor of Cancer Drug Target Discovery, hopes to prevent this.

Different pairs of feet

Danen became fascinated at an early stage in his career by the different types of receptor molecule that enable cells to adhere to a particular type of matrix protein. ‘It would be as if we could choose from different pairs of feet to walk down the same road.’ He and his group went on to show how tumour cells rapidly adapt if one class of these integrins, as they are called, is removed. The tumour’s adhesion reduces and its growth slows, but the cells become more active, allowing them to spread more efficiently. Danen is now looking for the junctions that are crucial to this adaptability of tumour cells. He hopes that this will lead to drugs that permanently destroy the tumour.

Mini tumour, grown with 3D cell printing
Mini tumour, grown with 3D cell printing

Large numbers of mini tumours

Danen and his colleagues and partners are developing innovative techniques that should help him answer his questions. Particularly spectacular is the development of cell-printing techniques that make it possible to grow cells in a 3D environment, which means that cells behave in a much more realistic fashion than in a 2D culture on glass or plastic. The researchers use a robot to print nanodrops with tumour cells in an extracellular matrix, thus facilitating the growth of large numbers of mini tumours. These are all in precisely definite positions, which makes them easy to track with automated microscopy.  Special software automatically analyses these experiments.

Inhibit tumour interactions

This approach makes the large-scale testing of drugs possible, and has resulted in new candidate drugs for prostate cancer and sarcomas – tumours in connective tissue such as is found between organs. Danen and his team also discovered that the force that tumours exert on the extracellular matrix causes it to distort and that a firmer matrix stimulates the invasive growth of tumours. They are now testing inhibitors that inhibit this interaction between the tumour and the matrix. 

The cell-printing method also makes it possible to map the communication between various cell types from a certain tissue. Danen and his colleagues are now testing drugs that regulate the interaction between the cells of the immune system and tumour cells. He expects that further insight into the interaction between tumours and their environment will result in new therapeutic strategies.

Text: Rianne Lindhout
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