A new look into cancer's roots

Scientists revive study of stem cells' link to disease

March 19, 2007|By Chris Emery | Chris Emery,Sun reporter

Scientists hope that someday stem cells will cure diseases.

Pamela Joseph fears that cancer stem cells will kill her first.

As her doctors explain it, stem cells are the source of multiple myeloma, a blood cancer the 56-year-old Clarksville woman has been fighting since 2005. Stem cells might also be the reason that the cancer - which has killed one member of Joseph's family - is incurable.

The notion of stem cells as potential villains is counterintuitive, given their highly publicized promise for repairing damaged tissues and organs. But some experts say that certain stem cells may be just as good at restoring cancers that doctors are trying to eradicate.

Learning how to destroy cancer stem cells, they theorize, might lead to that most elusive of breakthroughs - the cure for cancer.

This is an old notion, only recently revived. Scientists first explored the cancer-stem cell connection nearly 40 years ago but abandoned it when the scientific techniques of the period weren't up to the task.

Now, however, advances in molecular biology and the current boom in stem cell research have spurred renewed interest in the idea - and renewed skepticism.

Scientists at the University of Maryland and the Johns Hopkins University are investigating cancer stem cells, making Baltimore one of the few hubs for the nascent science. In January, the Maryland Stem Cell Commission received four proposals requesting state funding for the research.

"This is a very hot topic," said Dr. Richard J. Jones, one of Joseph's doctors at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center.

To explain it, Jones compares cancer to a dandelion, that bane of the well-manicured lawn: the flawed adult cells that make up the bulk of a cancer tumor are like dandelion flowers. Like a lawn doctor mowing down the flowers, a cancer doctor uses chemotherapy and radiation to eradicate mature cancer cells.

But just as dandelion flowers return, so, too, does cancer because the offending root - cancerous stem cells - remains intact.

"We have some pretty good lawnmowers," Jones said of cancer treatments. "But they don't get at the stem cells."

The theory holds that cancerous adult cells come from a relatively small number of stem cells. The stem cells can renew themselves through cell division and generate a variety of cell types - properties that make them promising for treating disease.

The same attributes, however, may enable them to become tiny factories that feed and renew cancers.

Simple as the concept seems - stem cells produce mature cancer cells - studying it is a complex matter.

Researchers at the University of Toronto demonstrated in 1971 that only a small percentage of the cancerous cells taken from leukemia-afflicted mice could grow and divide. They called these "tumor stem cells."

Six years later, a group at the University of Arizona developed a way to culture human versions of the cells in the laboratory.

But technological limits prevented those scientists from completely separating stem cells from other cell types, much less proving that stem cells gave rise to mature cancer cells.

"There was a big debate about whether they were actually stem cells," said Anne V. Hamburger, a member of the Arizona team that developed the technique.

Just as importantly, the research failed to produce new therapies, said Hamburger, now a professor of pathology at the University of Maryland Greenebaum Cancer Center.

"The whole idea went out of fashion," she said. "There was no funding for that type of work, so I moved in other directions."

As other scientists followed suit, the research ground to a halt. "It disappeared," Hamburger said. "It was a little mystifying."

A couple of decades later, science caught up to the theory. Researchers developed methods for using antibodies - important proteins of the immune system - to identify and isolate different kinds of cells in the laboratory.

In 1997, John Dick of the University of Toronto made the first definitive identification of cancer stem cells in leukemia. In 2003, Dr. Michael Clarke, now of Stanford, first isolated them from the solid tumors of breast cancer patients and showed that only cells with properties of stem cells generated new cancers.

Since then, cancer stem cells have also been found in brain and lung cancers.

But whether the cells are the source of tumors remains to be proven, according to Kenneth S. Zaret, a cell biologist at Fox Chase Cancer Center in Philadelphia. "That's really the big question now," he said, adding that stem cells might produce some cancers but not others.

The source of cancer stem cells is also unclear, he said. They could start as stem cells or be mature cells that regain stem cell properties because of genetic mutations.

Dr. Martin D. Abeloff, director of Johns Hopkins' cancer center, said the reasons that cancers recur may be complicated.

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