Article On Stem Cell Reseach

Colon cancer arises from stem cells: study finds
Updated Mon. Nov. 20 2006 8:55 AM ET

Canadian Press

TORONTO -- Canadian scientists say they have evidence that shows colon cancer arises from stem cells specific to the tumour, a finding that could lead to more targeted treatments to prevent recurrence of the disease.

The discovery was made after cells from human colorectal tumours were implanted in specially bred mice, said principal investigator Dr. John ****, a senior scientist at the Ontario Cancer Institute at Princess Margaret Hospital in Toronto.

"We found that not every tumour cell is equally capable of sustaining tumours in the colon," said ****, who holds a Canada research chair in stem cell biology. "Colon cancer stem cells are the driving force initiating and sustaining these tumours."

"Since this is the heart of the tumour, you have to find and kill each of these colon cancer stem cells to truly cure the disease."

Stem cells are the building blocks of the body from conception, giving rise to every type of organ and tissue. Although it's not known when or from where they originate, cancer stem cells act in a similar fashion to their benign cousins, providing the foundation for at least some malignancies.

To see if stem cells were at the root of colorectal cancer, ****'s team began by taking samples of tumours surgically removed from patients' large intestines or other areas of the body where the cancer had spread. They broke the tumours down into individual cells, then implanted "millions and millions" of them into the capsule surrounding the kidney of each laboratory mouse.

In all, 17 mice were implanted - and all 17 developed tumours, said ****, explaining that the immune-deficient mice lack disease-fighting cells, so cancer can grow unchecked.

"Now we know that we can get human tumours growing in an animal and the tumour looks identical to the tumour that's growing in a patient," said ****, whose research was published Sunday in an advance online edition of the journal Nature.

Through painstaking work transplanting various numbers of tumour cells into mice, the scientists initially determined that colon cancer stem cells are rare - occurring at a rate of about one in 60,000 cells.

They then narrowed the search even further by testing the cells for the presence or absence of CD133, a protein on the surface of some cells, which has been implicated in some other types of cancer, among them brain and breast.

When the different cells were implanted in mice, only some of the animals got tumours.

"What we showed was we basically never got a tumour when we transplanted the CD133-negative cells," said ****. "And all of the mice that were transplanted with CD133-positive cells gave us tumours."

The researchers also found that the new tumours were comprised of both positive and negative CD133 cells, proving that both types originated from the initial transplanted cell.

In other words, the scientists had isolated colon cancer stem cells, which act as the seeds from which the cancer grows. And they discovered they are actually rarer than initially thought, making up just one in every 250 cells in a malignant growth in the large intestine.

Based on this discovery, scientists can now begin to identify unique genetic properties of colon cancer stem cells and then develop drugs targeting these characteristics to prevent the disease from recurring.

"Everybody understands that if you get colon cancer, the big risk is that it could come back," **** said. "Cancer can relapse and colon cancer regrettably is one of those cancers that has a high rate of relapse."

"So it could be that the chemotherapy that we're using today is not targeting these cancer stem cells properly. And it's these cancer stem cells, because they're not targeted, they survive the chemotherapy."

Colorectal cancer is the second most deadly malignancy among Canadians after lung cancer, Canadian Cancer Society figures show. An estimated 20,000 men and women will be diagnosed with colorectal cancer this year, and 8,500 will die of the disease.



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