Our topic goes into malignancies. And we will talk
about those things that we were referring to earlier.
What is the thing that you are worried
about the most in malignancy?
All that increased proliferation of your cell like crazy.
Tell me about your nuclear to cytoplasmic ratio.
Increased. Why? Because of all that mitosis.
Remember that picture that I showed you with the metaphase,
where all the chromosomes lined up in the middle.
And it gave it that dark little unique structure.
Let me walk you through this.
On your left, is a transformed cell and you could have
many hits. Maybe it's a p53 type of mutation.
Maybe it's a BRAF. So on and so forth. As the
cell continues to grow and proliferate,
and it becomes malignant. You are going to move
to the right. Let me give you an example
what this organ might be so that you clearly
understand what is going on here.
This is extremely important. We'll go ahead and
call this a colon, okay? A colon.
On your left, is the lumen of the colon. As you move to the
right, what's happening is that the cell is proliferating.
You see that basement membrane. At that basement membrane,
you will notice that if there is enough proliferation,
you will go from what's known as in-situ.
So, what's the difference between in-situ and metastasis?
In-situ would be the membrane intact, you'll notice please,
that the cell is busting right through that basement
membrane. Penetrating right through there.
Give me some basics in biochem. The basement membrane is
made up of? What kind of collagen? I,II,III,IV or V?
IV for the floor. Amazingly, these cancer cells are well
equipped. They will bust through that basement membrane
by using the enzyme called collagenase. What type?
Type IV. Now you've passed through the membrane,
now you're ready for metastasis unfortunately. So,
now you will get through the interstitium.
And you're headed to a vessel. What kind of vessel might this be?
What is this highway that I was referring to earlier?
This huge vessel. Could be either blood, hematogeneous or
it could be lymphatic. It does'nt matter.
Point is, at this point, I want you to
understand the concept of metastasis.
So far, increased proliferation, malignancy. We
have a increase in nuclear to cytoplasmic ratio.
With increased proliferation, you are worried
about the membrane then becoming ruptured.
This brings you to what kind of measurement?
Staging or grading? Good. Staging.
Invasion, in order for you to invade you have to bust
through your membrane. Welcome to collagenase.
You continue moving forward and then you get through
the basement membrane on the other side
and you'll notice that, let's say this is at the colon.
And you are passing through your portal vein.
We will go ahead and call this a portal vein.
It will then metastasize to where? Think please.
From the colon to the liver. And then once it gets
to the liver. Well, in order to get there
you have to pass through the membrane again. And then
in the interstitium, you are then going to bind
to different types of components within the
interstitium. One of them being fibronectin.
Now that you've set up a new colony,
what do you need to do?
You need to then set up the infrastructure.
What's infrastructure mean to you?
Infrastructure means increased proliferation
and increased demand of oxygen.
So what do you need so that you can provide
the oxygen for the new colony? Good.
You need angiogenesis. What's the growth factor here?
VEGF. Vascular endothelial growth factor.
And do you know of any drugs that inhibit VEGF? Of
course you do. And if you don't, know it.
It is known as bevacizumab. A drug that knocks out
your VEGF. If you don't have angiogenesis
what happens to those cells theoretically?
They die. Literally they will suffocate.
Invasion and metastasis. Let's go into further detail.
Ability to metastasize defines a tumor as it becomes
more malignant, increased proliferation. I want you
to take a look at this picture at the very top
and we are now organizing it further. You find increased
proliferation, take a look. The membrane has now ruptured.
You find showering of cells into the interstitium.
How did that occur? Collagenase.
You broke through the membrane. Then, you are
making your way to the vessel.
In this case, I will go ahead and call this the
portal vein. You go through the basement membrane,
you get into the portal vein, hematogeneously where are
you going to spread if this was colorectal cancer?
To the liver. Once it gets to the liver, it will pass
through the membrane, and then it will bind to fibronectin,
increased proliferation, angiogenesis and growth factor.
At least know this much before we move onto further
discussions of malignancy and metastasis.