Cancer Researchers Find Unique Enzyme in Tumors : Health: Telomerase allows diseased cells to proliferate, study says. It may hold key to better anti-cancer drugs.
In a finding that opens the door to the development of less toxic, more effective anti-cancer drugs, and perhaps to new drugs to prevent aging, researchers at a Northern California company have discovered that virtually all human tumors contain a unique enzyme that blocks the biological clocks of tumor cells, allowing them to grow and proliferate virtually forever.
Normal cells, which do not contain the enzyme, lose a little bit of their DNA every time they divide, weakening them and eventually forcing replication to grind to a halt.
But in the presence of the newly discovered enzyme, called telomerase, the DNA of tumor cells is refreshed and renewed with every division, liberating them from the normal aging process.
The occurrence of the enzyme in ovarian cancer cells was reported earlier this year, but that report was greeted with some skepticism, said molecular biologist Al Rabson of the National Cancer Institute. Now a team at Geron Corp. in Menlo Park reports today in the journal Science what Rabson calls “much more impressive evidence” that telomerase is present in virtually every human tumor they studied.
The company has already identified several chemicals that block the action of telomerase and hopes to begin testing them in people within two years.
The advantage of this approach, researchers said, is that most human cells do not contain the enzyme and thus would be immune to any effects of the inhibitors. Furthermore, because the unusual enzyme seems to be present in nearly all tumors, any agent that could incapacitate the enzyme would work, theoretically, in all types of cancer.
“This has got the properties you’d be looking for in a magic bullet,” said molecular biologist Huber Warner of the National Institute on Aging.
Conversely, if researchers could induce healthy cells to begin manufacturing the enzyme, it might retard the aging process, particularly in highly vulnerable cells such as those in the brain.
“This is certainly a finding that will stimulate a great deal of interest in researchers studying the basic biology of aging, as well as cancer,” said gerontologist Richard Hodis, director of the National Institute on Aging. “Long term, our best hope for (halting aging) will depend on a better understanding of the biology of these systems.”
Scientists have long known that mammalian cells, unlike those of microorganisms, have a finite lifetime. When researchers attempt to grow them in the lab, the cells replicate about 60 times before they mysteriously die out.
Studies by a variety of researchers, especially biologist Elizabeth H. Blackburn of UC Berkeley, have shown that the key to immortality in microorganisms is a long fragment of DNA, called a telomere, that sits on the end of each cell’s chromosomes like the tip of a shoelace. Chromosomes are packets of DNA that contain the blueprint for reproducing an organism, and researchers now believe that telomeres keep the DNA stable, just like the tip keeps the shoelace from fraying.
The telomere represents a kind of bookkeeping device that controls aging. Each time a cell replicates, a fragment of the telomere is broken off and lost. When the whole telomere is gone, the chromosome breaks down and the cell dies. Microorganisms were found to have an enzyme--telomerase--that replaced the broken-off fragments, allowing the cells to continue thriving forever.
Today’s paper in Science now shows that virtually all human tumors contain the enzyme as well.
“This is a gorgeous example of a case where you begin with basic research on a microorganism and it turns out to have profound implications for human disease,” Rabson said.
In the new study, researchers at Geron and the University of Texas Southwestern Medical Center in Dallas used a new, highly sensitive test to show that telomerase was present in 98 of 100 human tumor cell lines grown in the laboratory and in 90 of 101 tissue samples from 12 types of human tumors. Conversely, the enzyme was not present in all 22 healthy cell lines grown in the laboratory and in all 50 biopsy samples that proved to be healthy.
“These findings provide the strongest evidence to date that telomerase is linked to cell immortality and cancer,” said molecular biologist Calvin B. Harley, a Geron vice president.
Geron was formed two years ago specifically to take advantage of discoveries involving telomerase, and the research has been supported by $30 million in venture capital. Scientists are now isolating chemicals that block the action of telomerase. Such drugs would not kill tumor cells directly, but would halt their growth and render them more susceptible to attack by conventional chemotherapy.
