Gene Stops Lung Cancer in Its Tracks
Prevents its spread and aggressiveness, Taiwanese scientists finds
TUESDAY, Sept. 18, 2001 (HealthDayNews) -- Taiwanese scientists say they've discovered a gene that appears to slow the advance of cancerous lung cells.
When present, the gene, called CRMP-1, retards the spread of lung cancer. Moreover, when added to tumor cells in a dish, it cuts their invasiveness by about half, the researchers say. The findings are reported in the Sept. 19 issue of the Journal of the National Cancer Institute.
The first invasion suppressor gene, NM23, was discovered about 15 years ago in mouse melanoma cells. Patricia Steeg, a pathologist at the National Cancer Institute who found that gene, says that since then the field has made only creeping progress.
Researchers "are not moving fast enough toward therapy," says Steeg, who adds that divining the function of these instructions is "painful work."
But Steeg, author of an editorial accompanying the journal article, is convinced that invasion suppressor genes hold promise for cancer patients with a variety of tumors.
"Our vision is to treat cancer as a chronic disease, the way we treat people with diabetes and arthritis," Steeg says. "While not a cure for cancer, I see this as a very valid approach" to treatment.
By the time a woman knows she has breast cancer, for example, and walks into the surgeon's office, her cancer may already have spread, Steeg says. "But can we halt [it] there?"
When cancer spreads, in a process called metastasis, cells from the primary site -- be it the breast, lung, liver or elsewhere -- travel through the bloodstream or lymph system and invade healthy tissue in another organ system. There they set about dividing unchecked until they displace the normal cells.
The why and where of metastasis is complex and not well understood, Steeg says. It may involve not only the failure of genes that normally quash itinerant cells, but signaling from distant sites to attract those nomads when they leave their base.
Danny Welch, a Penn State pathologist who studies metastasis, says understanding the process of cell movement can have a major impact on cancer care.
"It is a new field, but the promise is huge, because what kills people is when the tumor cells spread. If we can get a handle on that, the ability to cure [patients] is tremendously higher," he says.
In the latest study, a team led by Jin-Yuan Shih of National Taiwan University Hospital in Taipei isolated CRMP-1 from a pool of 9,600 other genes expressed in various colonies of lung carcinoma cells. CRMP-1 is short for collapsin response mediator protein-1, a molecule with a variety of potential roles related to cell development and growth.
The team found that when they added CRMP-1 genes into cancerous lung cells in a dish, the tissue became much less likely to invade neighboring cells. Cells with more gene activity were rounder and had fewer extensions linked to metastasis.
The researchers then looked for CRMP-1 in tumor samples from 80 people with lung cancer. Patients whose cancers had higher levels of the gene had less aggressive disease and less spread of tumor to their lymph nodes. They also went almost twice as many months after surgery before recurrence -- about 30 months vs. 16 in those with low levels of CRMP-1 -- and survived longer with their disease.
"We found that expression of CRMP-1 affects the invasive activity of lung cancer cells" in a lab study, and that "its expression is related to tumor stage, lymph node metastasis, and survival of patients," the authors write.
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