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Normal Cells May Predict Cancer Virulence
Date:8/28/2008

Finding suggests that treatment that only aims at malignant cells might fall short

THURSDAY, Aug. 28 (HealthDay News) -- Characteristics of normal cells which are present long before any tumor appears may determine how virulent a particular cancer is going to be, new research suggests.

Such cells may travel early on to distant sites in the body, residing innocently there until certain cancer genes are turned on.

"It's definitely conceptually very profound," said Dr. Katrina Podsypanina, a senior research scientist at Memorial-Sloan Kettering Cancer Center in New York City. "Our data seems to point toward the inherent decision that is made when the tumor is formed whether it is highly malignant or not. Moreover, since the characteristic might be dependent on the normal cell status, one might imagine that they might be different between individuals."

The study's senior author is Harold Varmus, who won the 1989 Nobel Prize for his work in cancer genetics and later went on to become director of the National Institutes of Health.

The finding implies that treatments that only target malignant cells may not be effective.

So far, however, the findings have only been shown in mice, and the research involved certain processes that were imposed which wouldn't normally occur in the human body.

"This does suggest that cells can sit for a long time, then be activated," said Dr. Claudine Isaacs, director of the clinical breast cancer program at Georgetown's Lombardi Comprehensive Cancer Center in Washington, D.C. "But these cells were injected into the circulation. Normal breast cells are not supposed to be in the circulation."

Also, the normal cells didn't form tumors until activated.

Conventional medical wisdom holds that the spread of a cancer occurs relatively late in the life of a cancer, happening only after cells from the primary tumor have undergone enough mutations to switch on different cancer genes.

Podsypanina and her colleagues performed a series of experiments in mice.

First, they injected normal mammary cells that contained cancer-inducing oncogenes, which could be switched on and off. These cells migrated through the bloodstream to the lungs, residing there for four months. They did not begin to grow aggressively until the oncogenes had been turned on, but they did so without first going through the stage of being a primary tumor.

Next, they injected normal cells without manipulating any oncogenes.

"Cells that did not have any oncogenes in them and do not transform spontaneously as per all published studies, we could see little colonies of these cells when we inspected the lungs," Podsypanina said. "At no point, never, did we see a solid vision that would resemble metastatic colonies, [but] it appears that every time we looked at the animal, the colonies appeared to be larger."

When these normal ectopic cells were injected back into a new generation of mice, they developed into normal mammary glands.

"It's a beginning," Podsypanina said. "It's an important step to show whether or not the first step of the metastatic cascade is something a normal cell can accomplish."

More information

Visit the American Cancer Society for more on oncogenes.



SOURCES: Katrina Podsypanina, M.D., Ph.D., senior research scientist, department of cancer biology and genetics, Memorial Sloan-Kettering Cancer Center, New York City; Claudine Isaacs, M.D., director, clinical breast cancer program, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, D.C.; Aug. 28, 2008, Science


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