title: Promoter hypermethylation of the cysteine protease RECK may cause metastasis of osteosarcoma.
abstract: 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.
authors.affiliation: Department of Orthopedics, Qihu Hospital, Shandong University, Jinan, 250000, China.|Department of Orthopedics, Yantaishan Hospital, Yantai, 264000, China.
authors.forename: Leisheng
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Yantaishan Hospital, Yantai, 264000, China.
authors.forename: Junbo
authors.initials: J
authors.lastname: Ge
authors.affiliation: Department of Orthopedics, The People's Hospital of Qixia, No. 259, Minsheng Road, Qixia, 265300, China. tianma_hospital@aliyun.com.
authors.forename: Tian
authors.initials: T
authors.lastname: Ma
authors.affiliation: Department of Orthopedics, Qihu Hospital, Shandong University, Jinan, 250000, China.
authors.forename: Yanpin
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Orthopedics, Yantaishan Hospital, Yantai, 264000, China.
authors.forename: Shiqiao
authors.initials: S
authors.lastname: Lv
authors.affiliation: Department of Orthopedics, Yantaishan Hospital, Yantai, 264000, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Yantaishan Hospital, Yantai, 264000, China.
authors.forename: Shaoxian
authors.initials: S
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D058851:GPI-Linked Proteins / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D011401:Promoter Regions, Genetic
chemical_list: D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; C115460:RECK protein, human; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Bone tumors; Metastasis; Osteosarcoma; Promoter hypermethylation; RECK