Matriptase and MET are prominently expressed at the site of bone metastasis in renal cell carcinoma: immunohistochemical analysis.

Matriptase and MET are prominently expressed at the site of bone metastasis in renal cell carcinoma: immunohistochemical analysis.
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DOI:
10.1007/s13577-014-0101-3
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发表时间:
2015-01
期刊:
影响因子:
4.3
通讯作者:
Kataoka, Hiroaki
Kataoka, Hiroaki
中科院分区:
生物学3区
文献类型:
--
作者:
Mukai, Shoichiro;Yorita, Kenji;Kawagoe, Yukari;Katayama, Yuichi;Nakahara, Kozue;Kamibeppu, Toyoharu;Sugie, Satoru;Tukino, Hiromasa;Kamoto, Toshiyuki;Kataoka, Hiroaki

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据报道,肾细胞癌(RCC)中的高MET表达和骨转移中的MET激活在几种癌症的进展中很重要。为了寻找骨转移的新治疗靶点,我们用免疫组织化学方法分析了MET和基质酶(肝细胞生长因子特异性细胞激活因子)的表达水平。我们获得了17例转移性肾细胞癌患者的肾切除术标本,以及7例转移性肾细胞癌患者的骨转移标本,这些患者于2008年至2012年在我院接受了转移性肾细胞癌切除术。我们用抗人MET多克隆抗体和抗人基质酶多克隆抗体检测样品,比较阳性组和阴性组的术后总生存率。在8/17(47%)的肾切除标本和6/7(86%)的骨标本中,MET在原发部位高表达。6/17例(35%)肾切除标本和7例(100%)骨标本中均表达基质酶。有趣的是,基质酶在5/7骨标本的破骨细胞中强烈表达。MET -组术后OS率明显高于MET+组。骨转移过程中,RCC细胞中MET和基质酶的高表达伴随着破骨细胞中基质酶的表达,表明它们在骨转移过程中的重要性。
High MET expression in renal cell carcinoma (RCC) and MET activation in bone metastases are reportedly important in progression of several cancers. To find new treatment targets in bone metastasis, we immunohistochemically analyzed expression levels of MET and matriptase (specific cellular activator of hepatocyte growth factor). We obtained nephrectomy specimens from 17 RCC patients with metastasis, and bone metastases specimens from 7 RCC patients who underwent metastasectomies, and who were treated at our hospital between 2008 and 2012. We tested the samples with anti-human MET polyclonal antibody and anti-human matriptase polyclonal antibody, and compared postoperative overall survival (OS) rates between positive and negative groups. High MET expression was seen at primary sites in 8/17 (47 %) nephrectomy specimens, and 6/7 (86 %) bone specimens. Matriptase was expressed in 6/17 (35 %) nephrectomy specimens, and all 7 (100 %) bone specimens. Interestingly, matriptase was strongly expressed in osteoclasts of 5/7 bone specimens. Postoperative OS rate was significantly higher in the MET− group than the MET+ group. The high MET and matriptase expression seen in RCC cells in bone metastasis accompanied by matriptase expression in osteoclasts indicates their importance in bone metastasis.
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