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Cancer stem cells might hold clue to melanoma growth

Killing cells fights tumors in lab mice

Email|Print| Text size + By Carey Goldberg
Globe Staff / January 17, 2008

In a key step from theory to possible treatment for melanoma patients, scientists in Boston report today that they were able to beat back a deadly human skin cancer in mice by targeting and destroying stem cells in the tumors.

The findings on malignant melanoma add weight to the growing belief among scientists that many types of cancer recur after treatment because small, resilient groups of stem cells survive and start multiplying again.

The research, published in tomorrow's journal Nature, shows that attacking melanoma stem cells is enough to halt a tumor's growth, said Dr. Markus Frank of Children's Hospital Boston, senior author on the paper. It thus offers new hope that this strategy will also work in humans - perhaps, researchers say, within just a few years.

"If this works with melanoma, this may also work with other tumors that are notoriously difficult to treat" once they have spread, said Dr. George Murphy, an author of the paper and chief of skin pathology at Brigham and Women's Hospital.

For more than a decade, scientists have been researching the theory that stem cells might be the worst villains in cancer, and the work has gathered momentum as stem cell populations have been discovered in cancers ranging from brain tumors to leukemia. Under a microscope, stem cells look like other cancer cells, but they can drive the growth of cancerous tumors in much the same way that normal stem cells can regenerate the body's healthy tissues

The paper is exciting and well done, said Dr. Peter Dirks, researcher of stem cells and brain tumors at the University of Toronto who was not involved in the work.

He cautioned, however, that this latest study, as well as others on cancer stem cells, are only preliminary, and it remains to be seen how broadly applicable the results are. Also, much of the work still awaits replication by other labs, he said.

"It's relatively early stages," he said, though he says he understands why the whole idea of cancer stem cells has recently "hit prime time: Because if you could treat those cells, maybe we'd have more effective, more long-lasting, more definitive cures for cancer. This [new] study is definitely a step in that direction."

One other concern that must be addressed with future research: whether killing the cancer stem cells brings with it "unexpected toxicity," hurting normal cells that use the same protein, said John E. Dick, also at the University of Toronto.

The study, whose first author was Tobias Schatton, focused on a protein lying on the surface of melanoma stem cells called ABCB5. Frank and his team, including his wife, Natasha Frank, had already shown that ABCB5 was a telltale marker for cells that could resist chemotherapy.

They set out to see whether melanoma cells that test positive for ABCB5 not only resist attack from treatments such as chemotherapy, but also serve as the seeds that then develop into more cancer.

What would happen, they wondered, if those nefarious cells were knocked out? Using monoclonal antibodies - molecular weapons that can hit highly specific targets - they went after the ABCB5-positive cells in human melanoma tumors grafted onto mice.

Tumor growth was "significantly inhibited," they report. Only three out of 11 mice developed new tumors, compared with 28 out of 28 mice whose cancer stem cells were left alone.

ABCB5 is actually a molecule that helps stem cells get rid of toxins - such as chemotherapy drugs - and thus helps tumors survive, Murphy said. "It's the very molecule that helps protect them that we have used to identify them."

Even if further experiments continue to look promising, it will likely be at least two or three years before the stem-cell strategy could start being tested in humans with melanoma, Frank said. But his lab will immediately try to develop the best possible antibodies for attacking melanoma stem cells, and will also use their findings to try to understand more about the biology of cancer stem cells, he said.

Malignant melanoma is the deadliest form of skin cancer, but it is easily treatable if caught early. Once it spreads, the disease is usually fatal. It kills an estimated 8,000 Americans per year out of a total 60,000 diagnosed.

Carey Goldberg can be reached at goldberg@globe.com

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