Natural secretion marks difference between mole and melanoma
Feb 8, 2008 - 3:29:37 AM
A protein naturally produced and secreted by the body can make the difference between your average mole and melanoma, which killed more than 8,000 people in the United States last year, reveals a new study in the February 8 issue of the journal Cell, a publication of Cell Press.
If this natural anti-cancer agent, called IGFBP7, can be produced and delivered to tumors, it might serve as a targeted chemotherapy for metastatic melanoma, a condition which is basically untreatable today, said Michael Green, a Howard Hughes Medical Institute investigator at the University of Massachusetts Medical School. It might also be used to treat other cancers with mutations in the oncogene known as BRAF.
This is a natural mechanism by which cells try to prevent cancer, Green said. The secretion of this protein gets lost in the formation of cancer. But, because it is secreted, it might also be converted to a therapeutic.
Mutations that leave BRAF permanently activated are found at high frequency in human cancers, the researchers explained. Such mutations are particularly prevalent in melanoma, where they occur in as many as 70 percent of cases. Those mutations, which are also found in some colorectal, ovarian and lung cancers, have been linked to cell proliferation and tumor growth.
Yet activating BRAF mutations are also present in up to 82 percent of benign moles (which go by the clinical term nevi). Pigmented moles progress to melanoma only very rarely, and studies have shown that the same BRAF mutations tied to cancer also cause pigment-producing human melanocytes to undergo senescence and cease dividing.
How, then, does an activated BRAF oncogene induce uncontrolled proliferation in melanoma and senescence in benign nevi? Green's team wanted to know. They suspected that melanomas might feature a second defect that inactivates the senescence otherwise induced in response to the mutant BRAF.
To find those factors, the researchers conducted a genome-wide screen of cells made to express the BRAF mutation (known as BRAFV600E) found in both melanoma and moles. They then disabled other genes in search of those that would allow the cells to begin dividing as they would in cancer.
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