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Cancer Stem Cells Created from Normal Prostate Stem Cells

Researchers reported that they have been able to break apart normal human prostate tissue, extract the stem cells in that tissue, and alter those cells genetically so that they spur cancer. This effort should provide a model for studying so-called “cancer stem cells,” i.e., cancer cells that develop from stem cells in the body and that are believed to be the origin of many cancers. This model may prove useful in understanding how cancers grow--and provide a new opportunity to test and identify novel cancer drugs. Many tissues contain pools of normal stem cells that replenish the tissue when it's damaged or when changes take place. For instance, stem cells in the skin produce new cells to replace those irreparably damaged by the sun, and stem cells in the breast create milk-producing cells when a woman is pregnant. The hallmark of these stem cells is that they self-renew. This means that in addition to making cells with a specific function, they also make many new stem cells. Mounting evidence suggests that these self-renewing cells are also tied to cancer. They tend to collect mutations, said Dr. Owen Witte, a Howard Hughes Medical Institute (HHMI) Investigator at UCLA, who was scheduled to present his group’s data on February 20, 2010, at the annual meeting of the American Association for the Advancement of Science (AAAS) in San Diego; and not much separates tumor cells, with their capacity for unchecked growth, from healthy, tissue-forming stem cells. "These cells have a huge capacity for self-renewal, and when the pathways that control self-renewal are augmented or changed, they can form tumors," Dr. Witte said.

Many scientists suspect that although tumors are made up of many cells, only the tumor cells derived from stem cells contribute to the growth of the tumor. For certain cancers, such as breast cancer and leukemia, that idea is well established. For others, such as prostate cancer, which Dr. Witte studies, the data are not conclusive.

Dr. Witte’s group is in the early stages of putting their new stem cell technique to use, but Dr. Witte noted that it offers some distinct advantages for developing new cancer drugs. At present, cells can be grown directly from a prostate tumor for use in experiments, but without knowing the precise genetics of those cells, scientists may never know why they became cancerous. Drugs that are effective in stopping their growth may not have the same impact on prostate tumors driven by different gene mutations. By contrast, because he has started by specifically altering normal prostate stem cells, Dr. Witte knows exactly which genetic changes have made a cell cancerous.

"Here you can preprogram the genetic buffet, and then evaluate a compound in the face of those specific changes," said Dr. Witte. That precision should speed the development of a new generation of fine-tuned cancer therapies. The new system should give scientists a firmer grasp of the genetic makeup of cells that are affected by particular compounds, and, by extension, help clinicians identify the drugs that will best help particular patients.

"The field of cancer research has produced a significant number of major new targeted therapies," said Dr. Witte. "Now we have to understand how best to use those therapies." [Press release]