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Four Genes Key in Breast Cancer Metastasis to Lung

Animal study shows that genetic, pharmacological approaches can almost halt metastasis

WEDNESDAY, April 11 (HealthDay News) -- The expression of four genes, which produce epiregulin, cyclooxygenase-2 (COX2) and the matrix metalloproteinases 1 and 2, collectively spur the growth of breast tumors as well as metastasis to the lung, according to a study in the April 12 issue of Nature. Animal studies suggest that blocking the genes with RNA interference or a combination of cetuximab (Erbitux) and celecoxib (Celebrex) may help prevent metastasis.

Joan Massague, M.D., of the Memorial Sloan-Kettering Cancer Center in New York City, implanted a human lung-metastatic variant of the MDA-MB-231 breast cancer cell line into mice. They used RNA interference to suppress expression of the target genes before implantation. They also tested the effects of cetuximab and celecoxib, which had previously been shown to act directly on proteins produced by the target genes.

The researchers found that silencing any one of the four genes was modestly effective at preventing metastasis, but that silencing all four of them almost completely eliminated tumor growth and metastasis. They also found that treatment with cetuximab or celecoxib alone was ineffective but that treatment with both drugs was highly effective.

"The genetic and pharmacological manipulation generated the same outcome, indicating that pharmacological treatment affects the activities of the four metastasis-progression genes only in tumor cells and not -- as has been assumed -- in cells of the tumor microenvironment, such as COX-2 in endothelial cells or MMP-1/2 in tumor-infiltrating inflammatory cells," states the author of an accompanying editorial.

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