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Scientists Create Breast Tumor Stem Cells

Achievement could spur research into cancer's spread, experts say

MONDAY, Aug. 13, 2007 (HealthDay News) -- U.S. scientists say they've succeeded in growing breast cancer stem cells from normal tissue.

Since it is suspected that these types of cells give rise to cancer's spread, isolating them could prove invaluable in the fight against the disease, experts say.

"There has not been any publication to my knowledge that has demonstrated a way to isolate these cells from human patients and expand them, meaning grow them in Petri dishes," noted study lead author Dr. Tan Ince, an "independent signaling investigator" at Brigham and Women's Hospital and an instructor at Harvard Medical School, both in Boston.

The findings, published Aug. 13 in the journal Cancer Cell, should help provide a common platform from which scientists can study these so-called tumor stem cells.

Making sure that tumor stem cells are similar between labs is crucial to advancing cancer research, Ince explained.

"Confirmation of results of one scientist by other independent scientists is critical for scientific progress, so it's important for different labs to have the choice to use similar or identical cell stocks," he said. "If two labs have different results, it is not possible to know whether this is a real difference or simply because different labs are using different cell stocks," he said.

However, "Until now, most labs that study human tumor stem cells had to use their own stock of cells, because it has been difficult to grow them in the Petri dish," Ince said. "We think this is what we accomplished and hope that this will allow different labs to compare their results much more easily with each other in the future."

Ince conducted the research while a member of the Weinberg Lab of the Massachusetts Institute of Technology's Whitehead Institute. Dr. Robert A. Weinberg, who discovered the first human oncogene in 1982, was senior author of this paper.

Recent research has suggested that not all cells in a tumor are created equal and that only some are capable of causing trouble.

"Tumor stem cells are cells that can initiate a whole tumor," Ince explained. "Experimentally, people have found that the vast majority, 99 percent, of the cells in the tumor cannot initiate a tumor in the next mouse. Only about one in a million does."

"You can imagine that if one of these dead-end tumor cells went to the lung or brain, they may not be consequential, whereas tumor stem cells are very aggressive and would be establishing a metastasis," he continued.

However, the work is cutting-edge right now, and not all scientists agree that tumor stem cells are at the root of most cancers.

Ince started out with the goal of making a mouse tumor that more closely resembled human tumors than those currently available.

"You want a mouse model that behaves like a human disease from the perspective of what genes are important to target and what drugs will be beneficial," Ince said.

To that end, Ince turned his lab into a sort of a kitchen and tried to improve the liquid media in which tissue is grown. The existing liquid media, he felt, was missing a number of vitamins, hormones and growth factors.

The final concoction contained 75 to 80 different ingredients.

"This took me close to two-and-a-half years. I had nothing to talk about all that time. People wondered what I was doing," Ince said.

But it paid off. He applied genes that had been used for years to transform normal tissue into tumor cells, and the tissue grew.

"The tumors looked much closer to what a human tumor looks like under a microscope," Ince said.

Then the Boston researcher noticed that the tumors he had grown in mice were growing in four to five smaller lumps, instead of one large lump, as is typical.

"That kind of pattern has been associated with metastasis in human patients, so that made me suspect that the tumors that I made with this new sort of cell might, in fact, have the potential to metastasize to distant organs," Ince said.

That's significant, because most tumor models used in the lab do not metastasize. In real life, however, it's these metastases that kill the vast majority of cancer patients.

Ince started injecting fewer and fewer cells into the mice and watching them for longer and longer.

"I still saw tumors when I went down to as few as 10 cells," he said. "Then I watched for 10 to 12 weeks, and I saw small metastases of several cells, micrometastases, in about 75 to 80 percent of the mice."

Ince realized that he had inadvertently created tumor-initiating cells.

The study also sheds light on how cancer cells evolve, the researchers said. Conventional wisdom has it that a normal cell undergoes a number of genetic mutations to eventually become cancerous. Now it appears that some normal cells are more susceptible to becoming cancerous in the first place.

Ince's culture medium, more than two years in the making, seems to favor the cells with high susceptibility.

In particular, this study may have implications for drug testing down the road.

"Until now, most of the drug testing had been done on standard tumor cell lines that only have very few tumor stem cells in them," Ince explained. "So, even if a drug killed 99 percent of tumor cells in a Petri dish, that would not have been a guarantee that this drug actually had killed any of the tumor stem cells."

But the new cells "will be much more useful to screen for new drugs that will specifically kill tumor stem cells [because a higher percentage are stem cells]," the investigator said. "The only thing in our way to test this hypothesis is a lack of funding that is particularly severe at this time, due to recent [U.S. National Institutes of Health] budget decreases."

More information

There's more on breast cancer at the American Cancer Society.

SOURCES: Tan Ince, M.D., Ph.D., independent investigator, Brigham and Women's Hospital, and instructor, Harvard Medical School, Boston; Aug. 13, 2007, Cancer Cell
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