Stem cells produce all of the tissues in our bodies.
When we are born, specialized stem cells maintain the health of specific tissues.
For example, our colon has specialized stem cells that keep our colon healthy by continuously
renewing the tissue.
They do this in a very elegant way!
In this depiction of our colon, the colonic stem cells are located at the base.
The stem cells will divide and produce cells that will move up until they slough off at
the top.
As the cells move up, they take on specific functions, such as absorbing nutrients into
our bloodstream, or secreting mucous needed for the tissue to function.
We call these differentiated cells.
Interestingly, we also find cells that resemble stem cells in some colon cancers, these are
called colorectal cancer stem cells.
So what are those?
Well, cancerous tumors are composed of all kinds of cancer cells.
In particular, certain cancers contain cancer cells that resemble stem cells.
It's important to understand that these cells are not identical to normal stem cells: instead
of recreating a tissue, like normal stem cells do, they can recreate an entire tumor.
Colon cancer is a type of cancer that is thought to arise from cancer stem cells.
It is the second-leading cause of cancer deaths and is currently treated with surgery and
chemotherapy.
However, after surgery, 30-50% of patients experience what we call "disease relapse"
where the tumor comes back and can be lethal.
There is often very little we can do when a tumor relapses because new tumors can occur
all over the body and can be hard to treat.
So from a therapeutic standpoint, we'd like to understand which patients are more likely
to experience tumor relapse.
However, we don't know much about what dictates colon cancer relapse...
The Batlle laboratory in the Institute for Research in Biomedicine in Spain wanted to
better understand what causes colon cancer relapse by examining what genes, or chunks
of DNA, are active in tumors from patients that eventually experience relapse compared
to those that don't.
Genes are chunks of DNA that produce protein.
However, genes only produce proteins when they are active.
The activity of genes dictates what sets of proteins are produced and in turn controls
how the cell behaves.
These scientists' findings are published in their article titled "the intestinal stem
cell signature identifies colorectal cancer stem cells and predicts disease relapse" published
in Cell Stem Cell in May 2011.
First, scientists determined what genes or chunks of DNA are active in normal, non-cancerous,
colon stem cells compared to differentiated cells of the NORMAL colon.
The sets of active genes in a cell is called a gene signature.
Next, the scientists looked at the sets of genes that are active, or gene signature,
of a variety of different patient tumors, looking at the DNA inside the tumor.
And what they found was that tumors from patients that eventually had relapse and the tumor
came back after surgery, had a gene signature that resembled that of colon stem cells (so
the genes that were active in the cancers that relapsed were similar to active genes
in colon stem cells).
On the other hand, tumors that didn't relapse after surgery had a gene signature similar
to differentiated normal cells.
So the next question is, is this stem cell signature, represented here in BLUE, in all
of the cells or only a subset?
When zooming into a tumor, the scientists found two types of cells: cancer cells that
resembled stem cell and cancer cells that resembled differentiated cells.
When injected into mice, only the cancer cells that resembled stem cells could make another
tumor whose architecture was identical to that of the tumor it came from: with cancer
stem cells and differentiated cancer cells.
Scientists could again take just the cancer stem cells of this new tumor, inject them
into mice again and those cells would produce a new tumor with the same organization!
This is proof that these cells that resemble stem cells are truly cancer stem cells because
they are able to make more of themselves over the long term and are able to produce differentiated
cancer cells.
So what can we take away from this?
Thanks to this study, we now know that colon cancer is driven by a special cell that resembles
a stem cell but has malignant properties: a cancer stem cell.
When we isolate these human cancer stem cells, they can produce tumors in mice that look
just like the tumor the cells came from, and looks a little bit like a disorganized normal
colon.
So could these cells be responsible for remaking a tumor in the case of relapse?
Yes, it's possible!
This study also tells us that the more the cancer gene signature resembles that of a
stem cell the more aggressive the tumor is and the more likely the patient is to experience
tumor relapse.
So what does this mean for you?
Using the gene signature of the tumor (is it stem cell like or does it resemble differentiated
cells?), we can now predict tumor relapse better than disease score can!
So this is very significant!
If two patients present to the clinic with colon cancer: one of them has a tumor with
a stem cell gene signature, the other doesn't.
The first patient is predicted to relapse more often.
In light of this new information, perhaps these 2 patients should get different cancer
treatments.
However, it is still unknown exactly why these cancer cells with a stem cell gene signature
are more likely to cause relapse?
As you can tell, we are now digging deeper into the tumor by examining DNA sequences
and what genes are active.
This will be the future of health care with personalized treatments based on a patient's
tumor genetic make up because not every cancer is created equal.