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Identification of Metastasis Suppressor Genes

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BackgroundMetastasis, the spread of cancerous cells from a tumor toalternate sites in the body, is a chief cause of death in patients with solidtumors.  These cells escape fromtumors in a multiple-step process: metastatic cells first need to cross the border of the tumor, then enterthe bloodstream, adhere to the blood vessel wall, and escape the blood vesselat a different site.  While manygenes that promote metastasis have been identified, the suppressors ofmetastasis until now have remained unknown.TechnologyDr. Michael Green and colleagues have identified suppressorsof metastasis using genome-wide shRNA screening technology (Gobeil et al. (2008) Genes Dev 22: 2932-2940).  shRNAs were expressed in B-16F0 mousemelanoma cells in a three-dimensional tissue culture system, and the cells wereassayed for new colony growth. Candidate shRNAs were used to make stable cell lines, which wereinjected into mice to examine lung metastasis.  The knockdown of 22 target genes resulted in increasedmetastasis, and 12 of these genes were found to be downregulated in metastaticcell lines.  Eight target genes(Cyclin A2, CDC26, GAS1, PPP1R10, CTSO, PCSK6, UQCRC2, and PRRG3U) are alsodownregulated in human metastatic melanomas.ApplicationPrevention of metastasis of tumor cells Competitive AdvantagesWhen activated or overexpressed, these genes have thepotential to specifically reduce the spread of cancerous cells.  This technology could be an importantaddition to chemotherapeutic regimens.

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美国