Melanoblasts (rainbow) in a mouse embryo skin moving over time. Credit: Emma Woodham and Nikki Paul
We all start life as a fertilised egg, but for this to develop into an embryo each cell has to go through a step-by-step process.
It’s a carefully choreographed journey that combines how cells divide and move.
And whether they’re destined to form the tip of a little finger or a sturdy big toe, these ‘young’ cells rely on lots of different molecules working together.
These molecules are vital to help the cells travel from a ball in the middle of the embryo, to their final destination, where they grow and mature.
Unfortunately, melanoma is particularly prone to metastasis so this is why it’s important we understand how these cells move.
– Professor Laura Machesky
Collectively these processes are called developmental biology, and Professor Laura Machesky, a cell biologist from our Beatson Institute in Glasgow, takes lessons from these cells and applies them to cancer. Working with cells from mouse embryos, her team studies how these ‘young’ cells move in search of links to how cancers spread.
“Developmental biology is really useful as the processes that happen during an embryo’s development are the same processes that cancer cells reactivate,” says Machesky.
According to Machesky, understanding exactly what happens as an embryo develops can give a “clear picture of what’s going on in cancer cells”.
And a new early stage study from the team, published in the journal Current Biology, sheds some light on how a molecule helps young skin cells move, which could tell us more about skin cancer.
Where melanoma starts
Melanoma skin cancer starts in cells called melanocytes. These are cells that make a pigment called melanin, which gives skin its natural colour.
Studies have shown that cancer cells backtrack to a ‘younger’ state, so Machesky’s team has turned to melanoblasts (cells in an embryo that will become melanocytes) to give them clues as to what happens when melanoma spreads (metastasis).
“Unfortunately, melanoma is particularly prone to metastasis so this is why it’s important we understand how these cells move,” says Machesky.
The team has now uncovered a key set of controls in ‘young’ skin cells (melanoblasts) that may be in charge of the cells’ ‘feet’.
This is what ‘cellular feet’ look like:
“Here are normal melanoblasts moving in a mouse embryo’s skin. Each dot is a melanoblast moving around. The little spikes are their pseudopods,” explains Machesky.
“A pseudopod is a protrusion a cell makes. It’s like putting your foot forward. When it moves it plonks its foot down and uses it to pull itself along.”
Understanding the signals that allow melanoma cells to move will help scientists identify the best way to trip them up and stop them from travelling to other areas of the body.
And Machesky thinks that the best way to stop cells moving is to make sure they can’t put one ‘foot’ in front of the other.
CDC42 is one of the many molecules inside a melanoblast that helps it travel in the right direction.
“CDC42 helps the embryo organise itself,” says Machesky. “It helps melanoblasts know where their front and feet are. When CDC42 is blocked the cell’s asymmetry is disrupted, so now it’s like having a head and foot on both sides.”
Switching off CDC42 in mouse embryo cells ruins their coordination so they can’t distinguish the front from their back, which, as this clip below from the lab shows, makes it very hard for them to move.
“When you’re walking you have to move your feet and then put your shoulder in line and swing your hands, without CDC42 cells can’t do this, they have no coordination. They simply can’t put one foot in front of another.”
What does this tell us about cancer?
Researchers believe that CDC42 is an important molecule to study in cancer, as it has to be in good supply for cancer cells to spread and invade other areas of the body, based on lab studies and patient tumour samples.
This suggests that cancer cells need CDC42 to keep their feet moving.
Because scientists think embryo cells and cancer cells use the same molecules to move, they can use mouse embryo cells to understand how molecules like CDC42 work. This will point to clues as to how cancers, like melanoma, spread.
And as the development of cells in the skin of mouse embryos is carefully choreographed, with only a few things happening at once, the impact that molecules like CDC42 have on a cell, its shape and how it moves can be followed carefully in the lab.
“Cancer is so chaotic,” says Machesky. “A whole bunch of things go on at one time. An embryo is much more logical so it’s easier to see what’s going on.”
So looking at the inner workings of these ‘young’ cells in mice embryos helps scientists understand how cells like melanoblasts move. And if the same controls are found to help melanoma cells spread, this could point to ways to trip them up for good.
Woodham E. F. (2017) Coordination by Cdc42 of Actin, Contractility, and Adhesion for Melanoblast Movement in Mouse Skin. Current Biology. DOI 10.1016/j.cub.2017.01.033