Using human cell lines in experiments with mice, a team of researchers at Penn State's College of Medicine have isolated and characterized a gene, designated Breast-cancer Metastasis Suppressor 1 (BRMS1), that plays a role in blocking tumor cells' ability to spread and colonize secondary sites.
Danny R. Welch, Ph.D., associate professor of pathology and leader of the Penn State team, says, "The gene provides a target to develop therapies that keep cancer localized. Initially, it may also be helpful for making proper diagnosis."
Welch and co-authors published their findings in the current (June 1st) issue of the journal, Cancer Research, in a paper, Functional Evidence for a Novel Human Breast Carcinoma Metastasis Suppressor, BRMS1 encoded at Chromosome 11q13. The co-authors are Dr. M. Jabed Seraj, former postdoctoral fellow now at the Department of Urology, University of Virginia; Dr. Rajeev S. Samant, postdoctoral fellow and Dr. Michael F. Verderame, assistant professor of medicine.
Welch's research group had previously shown that the introduction of a normal human chromosome 11 reduced the ability of a human breast cancer cell line to spread or metastasize by 70 to 90 percent, suggesting the presence of one or more suppressor genes on that chromosome. Other laboratories have estimated that between half and two thirds of patients with late stage breast cancer lose copies of chromosome 11.
By comparing cells containing the added chromosome 11, in which metastasis was suppressed, with metastatic breast cancer cells, the group found that BRMS1 was more highly expressed (i.e.. the gene is turned "on") in the nonmetastatic cells. They then cloned BRMS-1, introduced it into metastatic cells and showed in experiments with mice that BRMS-1 suppressed the ability of the breast cancer cells to metastasize to lungs and lymph nodes without affecting their ability to form a tumor in the breast.
Welch says the majority of cells within a tumor cannot complete the multistep process of metastasis. For cells to successfully metastasize, they must interact with a variety of host cells and then respond in the appropriate manner. If a cell fails to complete any of the many steps involved, it is nonmetastatic.
"It takes only one gene to block metastasis, whereas it takes many coordinated steps for metastatic disease to occur," he says.
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