RECK expression in osteosarcoma: Correlation with matrix metalloproteinases activation and tumor invasiveness
RECK expression in osteosarcoma: Correlation with matrix metalloproteinases activation and tumor invasiveness
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DOI：
10.1002/jor.20323
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发表时间：
2007-05-01
影响因子：
2.8
通讯作者：
Han, Ilkyu
中科院分区：
文献类型：
--
作者：
Kang, Hyun-Guy;Kim, Han-Soo;Han, Ilkyu
骨肉瘤是一种骨的恶性肿瘤，其特点是高转移潜能。对于转移的发展，需要基质金属蛋白酶（NIMPS）的活化。一种新的MMPs抑制剂，具有Kazal基序的逆转诱导富含半胱氨酸的蛋白（RECK），已知在许多肿瘤衍生的细胞系和某些类型的肿瘤中下调MMPs并抑制侵袭和转移潜力。RECK在骨肉瘤中的表达及其在肿瘤侵袭中的作用尚未见报道。我们用定量真实的时间PCR、明胶酶谱、侵袭实验和转染实验检测了RECK mRNA的表达和MMPs的活化。RECK在骨肉瘤细胞中表达下调。在所有样品中观察到MMP-2前体的活化，而MMP-2和MMP-9前体的活化分别仅在11%和7%的样品中检测到。MMP-9在任何样品中都没有被激活。RECK的表达水平与MMP-2原的活化呈负相关，转染RECK过表达可降低MMP-2原的活化，降低肿瘤的侵袭性。提示RECK在骨肉瘤的侵袭性中起重要作用。(c)2007骨科研究学会。
Osteosarcoma is a malignant tumor of bone characterized by its high metastatic potential. For the development of metastasis, activation of matrix metalloprotemases (NIMPS) is required. A novel MMPs inhibitor, reversion inducing eysteine 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. (c) 2007 Orthopaedic Research Society.