The present study examined the role of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) promoter hypermethylation as a causative factor in metastasis of osteosarcoma. Using human pathological samples, it is demonstrated that RECK, a cysteine protease that reversibly regulates expression of matrix metalloproteases like matrix metallopeptidase 9 (MMP9), is transcriptionally inhibited in osteosarcoma, especially metastatic variants. This result comes from its promoter hypermethylation, as evaluated in the present study by methylation-specific PCR reaction. The expression of RECK was also significantly diminished in the metastatic variants of osteosarcoma. This downregulation of RECK in advanced grades of osteosarcoma and metastatic grades was also associated with the increased expression of invadosome-specific markers like MMP9, phospho-FAK, and integrins, suggesting the complex contributions of RECK in the prevention of metastasis and its downregulation as a causative factor in osteosarcoma metastasis.
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