Sticky spots and Big Brother – Studying skin cells in the lab

Professor Fiona Watt is a leading expert in skin cancer

Our bodies are made of millions upon millions of tiny cells. One of the biggest challenges for researchers studying cancer is to find out what individual cells are doing as they change from a healthy state to a cancerous one. But many lab techniques only give an overview of a large population of cells, either in healthy tissue or a tumour.

To address this challenge, Cancer Research UK’s Professor Fiona Watt and her colleagues in Cambridge and the Netherlands have devised a clever technique to study individual skin cells. And this allows them to investigate exactly how solitary cells change in response to different situations.

First trap your cells…

Professor Watt and her team are experts in skin stem cells, the immortal ‘starter’ cells that produce the other cells in our skin. Scientists believe that skin cancer may be caused by these stem cells multiplying out of control.

Working with researchers at the University of Cambridge’s Chemistry Department, and publishing their results this week in the journal Nature Cell Biology, the scientists developed special surfaces covered with microscopic dots of a sticky protein called collagen. This acts as a kind of ‘Velcro’ for skin cells, encouraging them to stick to the surface specifically in those areas. These dots were only slightly larger than the diameter of a cell, so when the scientists put skin stem cells on the surface, only one cell stuck to each spot.

Once the scientists had trapped individual skin stem cells on the spotty surface, it was time to do some experiments. Similar to the way that TV programme Big Brother traps participants in a house, gives them tasks and watches how they react, the researchers treated their trapped cells in a variety of ways, and viewed the results down a microscope.

Under the microscope

The scientists were searching for things that affected differentiation – the process that happens as stem cells lose their immortality and turn into the other types of more specialised skin cells.  Problems with differentiation contribute to the development of skin cancer.

Professor Watt and her team discovered that cells trapped on smaller dots were less likely to differentiate than cells on larger ones, suggesting that the physical environment around a cell affects its behaviour.

They also found that switching off a gene called SRF using RNA interference prevented differentiation. Intriguingly, mouse skin cells lacking SRF tend to multiply out of control rather than differentiating, mimicking stem cell-like behaviour. This is similar to the transformation of healthy cells into cancer cells, so this finding could shed light on the processes at work during the development of skin cancer.

By discovering the conditions that cause skin stem cells to remain immortal or switch into differentiation, we can understand more about the triggers that cause healthy stem cells to become cancerous.

But, more importantly, the technique used by Watt and her team is an important step forward in studying individual cells and figuring out how they behave in response to different triggers and in different environments, and will be applicable to many different types of cancer. Progress in research depends on technological advances, so although this is a relatively small step, it holds great potential for future discoveries.

Kat

Reference:
Connelly, J. et al (2010). Actin and serum response factor transduce physical cues from the microenvironment to regulate epidermal stem cell fate decisions Nature Cell Biology DOI: 10.1038/ncb2074