use of proteases to actually cut these molecules, chop them so they can go
through. The action of these protease, this has to be highly regulated so you
should note that these molecules, the proteases are secreted from cells in an
inactive form, and they’re normally secreted along with inhibitors so you
secrete the proteases and also inhibitors of those proteases. Generally you
don’t want these proteases to work except in very specific circumstances. If
you sent out active proteases into the ECM, it would digest the entire ECM
and it would be gone. These inactive molecules are sent out into the
extracellular space and normally their activity is controlled by binding to the
surface of the cell that wants to use them. These inactive molecules will bind
to the surface of the cell & therefore be locally activated & very specifically
controlled. You have very specific digestion of the extracellular matrix where
you need a fibroblast to crawl through it or a white blood cell, etc.
- In addition to these cell types, this is also relevant to cancer progression. As
we’ll learn about and as we’re all aware, we will have a primary tumour and
then as cancer progresses, the cells will start to migrate away from that
primary tumour to other sites in the body. To migrate from the primary
tumour, those cells also have to travel through the extracellular matrix. They
also make use of proteases to do that.
- It is important to know about these proteases because there is the potential
to develop drugs to block the ability of cancer cells to travel through the
extracellular matrix so you might be able to slow down the progression of
cancer, stopping them from spreading through the extracellular matrix.
- That is just shown in the cartoon. There is a tumourous cell that is growing
and metastasizing, moving through the extracellular matrix. It is doing that
here because it has these uPA receptors being expressed so therefore it is
recruiting this protease called uPA to the surface of the cell and activating it
there. Now this cell will have active proteases coating its surface so when it
comes into contact with extracellular matrix, it can chop those proteins up
and travel through that extracellular matrix.
- On the other side, there is an inactive form of the protease that is being
expressed, this is competing away the normal protease so most of these
receptors on the surface of the cell are now bound to inactive proteases. You
can imagine in this case, this is a mutant form of the protease that
outcompetes the normal form but you could also imagine that these yellow
molecules could be a drug that could be given to a cancer patient. So you can
add a competitor of these active proteases that could compete with those
proteases for the receptor, basically bump them off the receptors & now this
cell here, it may still grow but it will be much more difficult for it to travel
through the ECM becoming more contained in the body, preventing
! (e.g. blood vessels, lungs)
- Now onto elastic fibres. These fibres also provide structural support but as
the name implies, they are elastic. These are abundant in highly flexible
tissues like blood vessels or lungs so that when your lungs expand, they will
snap back to their original position; when the blood vessel expands, it will
snap back to its original position.
- A number of our organs have this elastic property so elastin plays a key role
in this because it can recoil after tissue stretching.
- In the cartoon, we have the elastic fibre that can be stretched out and then
snap back afterwards.