Breast gene may slow the spread of cancer.

Tumor suppressor genes earn their name because when they work right, they seem to keep cell growth in check. When they stop doing their job, cancer can develop. Such is the case with the p53 gene, which guards against a variety of cancers (SN: 11/27/93, p.356).

Now, geneticists have found a tumor suppressor gene that may play a role only in breast cancer. Known as the maspin gene because it codes for the protein maspin, this gene's activity -- or rather inactivity -- may forewarn of cancer on the brink of spreading, says Ruth Sager of Boston's Dana-Farber Cancer Institute.

Sager's team discovered the maspin gene by first searching for differences in the genetic material in normal and cancerous breast cells. The researchers uncovered more than 30 genes for which the transfer of protein-production messages either did not occur or occurred at very low levels.

Maspin closely resembles substances called protease inhibitors. These inhibitors attach to specific enzymes, rendering them incapable of breaking down their target proteins, says Sager.

She and her colleagues observed that maspin disappears from breast cancer cells grown in the laboratory. The same proved true when they examined samples of healthy and cancerous breast and lymph node tissues, as well as airway fluids from women whose breast cancer had spread to the lung, they report in the Jan. 28 SCIENCE. Healthy cells that line the breast ducts contained maspin, as did those cells near a tumor. Breast tumors that had not yet spread made very little maspin, and almost no maspin existed in tumor cells obtained from the lung and lymph nodes. In these cells, the gene remained intact but inactive, Sager notes.

To search for maspin, the scientists constructed pieces of the protein and from those pieces made antibodies that would recognize and attach to maspin. They tagged the antibodies and with them detected maspin in normal cells and in tumor cells into which they had injected an activated maspin gene.

They then put malignant tumor cells -- some of which contained the activated maspin gene and some of which did not -- into mice bred to accept cells from other species. The mice receiving cells with the maspin gene developed smaller and fewer tumors than mice injected with maspin-free cancer cells. None of the tumors in the first group of mice spread to other sites, indicating that maspin slows tumor growth and invasion, or metastasis, into other tissues. "[Maspin] seems to have quite an important effect in inhibiting the invasion process," says Sager.

"If you could upregulate [increase] maspin production, it's potentially a new therapeutic direction," comments William Stetler-Stevenson at the National Cancer Institute in Bethesda, Md.

It seems that maspin leaks out of cells, somehow making them less able to move away from the tumor site, says Sager.

Sager's group has tested 10 other tissues and found no active maspin gene, leading her to suspect that maspin works just in the breast.