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UI researchers study how maspin inhibits breast cancer cell movement

IOWA CITY, Iowa -- Researchers at the University of Iowa College of Medicine are taking a lead role in understanding how a tumor suppressor gene called maspin (mammary associated serine protease inhibitor) controls breast cancer cell movement. Their findings could have a significant impact on how breast cancer, and possibly other cancers, are diagnosed and treated.

Maspin occurs naturally in the cells of normal breast tissue and helps maintain the normal state of the tissue. Its discovery was first reported by researchers at the Dana Farber Cancer Institute and Harvard Medical School in 1994, in collaboration with the laboratory of Dr. Mary J.C. Hendrix, UI professor and head of anatomy and cell biology. The researchers found that maspin slowed the growth and spread of breast tumors.

"Basically, when breast tissue cells lose maspin, they become cancerous," Hendrix says. "If a biopsy from a woman's breast sample contains maspin, that's a good sign -- it's probably a benign tumor. However, a biopsy that shows no maspin means that the cancer has more than likely progressed."

Early detection of breast cancer is crucial, Hendrix says, because evidence suggests that often at the time of diagnosis, many patients may already have metastases, the recurrent migration of tumor cells to other parts of the body. "In other words, these cancerous cells may already be on the move by the time they've been diagnosed," she says. "There is a need to identify additional ways to determine the extent to which the disease has progressed." One of the benefits of maspin is that researchers can detect its presence or absence in tissues by using antibodies to screen the biopsies of patients.

Understanding the biological mechanisms of maspin is the next step for UI researchers. Hendrix and her colleagues have recently received a five-year, $1.26 million grant from the National Institutes of Health to study how maspin stops tumor cells from moving. One thought is that it inhibits tumor cells from secreting certain proteases -- enzymes that are necessary for cancer cells to digest their way through blood vessel basement membranes in tissues. "It's good to know maspin keeps these cells from moving, but it's equally important to know how this occurs," Hendrix says.

Knowing "how" could lead to possible cancer treatments. LXR Biotechnology, Inc., a drug discovery and development firm based in Richmond, Calif., has developed a recombinant form of maspin that could someday be delivered to breast cancer patients who lack it. Biologically potent forms of maspin are being studied under the direction of Dr. Philip Pemberton, head of protein chemistry at LXR, who is collaborating with UI researchers.

"The overall goal is to stop the cancer cells in their tracks and induce them to die," Hendrix says. "What we hope to learn from this current study is that perhaps there is a certain stage of the cell cycle where we would need to introduce maspin for it to be most effective."

Preliminary observations from Hendrix's laboratory indicate that maspin may also be effective against prostate cancer, an area deserving additional study, she says.

Much work still needs to be done, Hendrix notes, but the potential for new cancer therapies being developed at the UI is solid. "This is a very promising product. If all goes well, we'll be the first institution to conduct clinical trials, in collaboration with LXR Biotechnology, perhaps within the next year and a half."

9/23/97