RECK expression in osteosarcoma: correlation with matrix metalloproteinases activation and tumor invasiveness.
Osteosarcoma is a malignant tumor of bone characterized by its high metastatic potential. For the development of metastasis, activation of matrix metalloproteinases (MMPs) is required. A novel MMPs inhibitor, reversion inducing cysteine rich protein with Kazal motifs (RECK), is known to down-regulate MMPs and suppress the invasive and metastatic potential in many tumor-derived cell lines and some types of tumors. The expression of RECK and its role in tumor invasiveness have never been studied in osteosarcoma. We examined RECK mRNA expression and MMPs activation in osteosarcoma using quantitative real time PCR, gelatin zymography, invasion assay, and transfection experiments. RECK was expressed but down-regulated in osteosarcoma cells. Activation of pro-MMP-2 was observed in all samples, whereas activation of MMP-2 and pro-MMP-9 was detected in only 11% and 7% of the samples, respectively. MMP-9 was not activated in any of the samples. The level of RECK expression was inversely correlated with pro-MMP-2 activation, and overexpression of RECK by transfection resulted in decreased pro-MMP-2 activation and reduced tumor invasiveness. These findings suggest that RECK plays an important role in the invasiveness of osteosarcoma.
Kang
Hyun-Guy
HG
Department of Orthopaedic Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea.
Kim
Han-Soo
HS
Kim
Kap-Jung
KJ
Oh
Joo Han
JH
Lee
Mi-Ra
MR
Seol
So Mi
SM
Han
Ilkyu
I
D001859:Bone Neoplasms / Q000201:enzymology / Q000473:pathology*; D004789:Enzyme Activation / Q000502:physiology; D058851:GPI-Linked Proteins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics*; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000201:enzymology / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; C115460:RECK protein, human; D012333:RNA, Messenger; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9