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.