So we all know by now cells can move, and they can move very well! Remember that nice curvy gliding lamellipodia on 2D or those spiky feet the cells make in 3D? Yeah, those are the structures that allow the cell to move. So sure the cells can move, but how do they know where to go to? They can't just wander off randomly, there has to be something that allows them to "see" where they are going, right? So let say you're an immune cell, and your body just got cut, and the bacteria from the outside world flush, trying to colonise the wounded part of your body. You as an immune cell reside in the surrounding tissue as well as in the blood needs to know where is this cut and so you can get there on time to kill off that infection, right? Turns out, there are certain chemicals that are released by the damaged tissue, these are called chemokines. They basically leave a trail that allows the immune cell to sniff along and follow the path to where the source is.
And yes, during disease processes, these chemokines turn out to be one of the reasons cancer can metastasise to distant body location. During the metastasis process, the cancer cells enter the bloodstream, floating about in here. Most of them will be dead due to the not-so-familiar environment these cancer cells have to deal with. However, just by the law of probability, the large number of these cancer cells in the bloodstream ensures that at least a portion of them will survive. That does not even consider the help of other blood factors such as the betrayal platelets, but that's a story for another time. When these circulating cancer cells detect a chemokine trail from an organ where suitable, they will start exiting the bloodstream, and migrate towards that heavenly spot for them to start growing. And that is how metastasis is formed.
But, what about at the beginning when the cells were still within a tumour, how do they know how to get out? I mean they were stuck inside a cocoon made out of their own flesh, a mass of compact cell bodies. Well, it turns out there are other signalling pathways that help them out as well. The first one has to be blood vessels. These tumour cells are insidious. They can stimulate nearby blood vessels to redirect towards them, supply them with food and a path to get out in a process called angiogenesis. They can even make a brand new blood vessel, a process called neoangiogenesis. And that is not it. The environment from within the tumour itself can also act as a stimulant too! O2 or oxygen for example. You can imagine living in the centre of a tumour must be so stuffy and it is. You lack nutrients, you lack chemokines, and you lack oxygen. These central cancer cells react to this using a protein called HIF1a. This leads to the activation of many genes, including those of neoangiogenesis and migration. I actually wrote a review about this process during my final year literature review with Professor Kate Nobes in Bristol and was so fascinated by such a simple yet sophisticated feedback process. That was also one of the reasons why I am so eager to learn more about how the surrounding environment can affect cancer, both in terms of migration and survival. Look at the video below that I made.
This was one of those experiments that I did out of curiosity, it didn't work as intended, but I think it demonstrates strikingly how the cancer cells within that blob of cells in the middle know where is the outward direction to go to! You can see the cyan spheroid in the middle of the dish is so quick to dissipate, the cells within it just spread into the surrounding like a tidal wave, even pushing away those magenta cells around. If you colour these cells with a different shade of colour at different time points, you got something like this:
I call this image the "Glowing sun". This is also the same image that got me the third place in our annual Beatson Image Competition.
So yeah, I hope now you know a bit more about how the cancer cells metastasise. And by knowing this, hopefully, we can develop some therapeutics that can intervene with this deadly process and stop them on their track, so all they can be is just a pretty picture!
Until next time :)
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