Cancer cell plasticity: a molecular horror story

This post originally appeared on my PhD student group blog and you can find it here. Please take the time to go over and check it out – it’s a fantastic blog with lots of exciting things going on!

In 2012, over 160 thousand people died from cancer in the UK. Of these, about 90% were a direct consequence of the tumour spreading to new organs. Cancer cells move around the body and form new tumours in areas far away from where the cancer started. For example, breast cancer cells can end up in the liver and skin cancer cells can form new tumours in the lung. This deadly process is known as metastasis and is entirely dependent on the ability of cancer cells to move.

In fact, during the course of the disease cancer cells move away from the main tumour and invade the nearby tissue until they encounter lymph and blood vessels and blood capillaries. Metastasising cells then squeeze themselves into these vessels, entering the blood stream that will carry them all over the body and give them access to every organ. Ultimately, tumour cells get out of the blood vessels, entering a new tissue where they will form new tumours or metastases.

The whole process of metastasis is clearly dependent on the ability of cancer cells to move, or migrate. Cancer cells invading tissue can move either in groups or as individuals. Contradicting the old adage that there is strength in numbers, cells originating from most cancers need to be migrating as individuals to successfully form metastases. What’s more, cancer cells moving as individuals have the ability to “switch gears”. This process is especially clear in cells from melanoma, the most deadly form of skin cancer.

Melanoma cells migrating through tough tissue, such as bone, adopt the cellular equivalent of a low gear on a car. A car in a low gear will move slower, but more efficiently through difficult territory such as a muddy field or a steep incline. A melanoma cell using a low gear will change its shape to an elongated outline, known in the field as a spindle. These cells move by grabbing firmly onto the fibrils that make up tissue and pulling themselves through the gaps between these fibres.

On the other hand, melanoma cells that are moving through softer tissue can switch to a higher gear in the microscopic equivalent of driving on the motorway. Cells in high gear are known as rounded-amoeboid cells because they switch to a rounded shape reminiscent of an amoeba. These cells move by contracting so violently they stretch out the tissue they are migrating through, making it possible for them to move on. Disturbingly, these cells can also secrete molecules that corrode the surrounding fibres, forming holes in the tissue through which they can invade new territory.

The inner workings of a cell are regulated by a an intricate set of blueprints that originate in the cell’s DNA, sensitive to the smallest signals from the outside world and fine-tuned by a huge variety of complex chemical processes. Cell biology as a field can be thought of as trying to decipher these blueprints and understand how they control the life of a cell. In particular, we are currently trying to understand how melanoma cells can switch gears. Like with most medical research, the idea is that once we fully understand this process we should be able to make drugs that can block it.  This mechanism has large-scale consequences, as the ability to switch to a high gear directly affects how well melanoma cells can invade tissue, enter blood vessels and form metastases.


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