Mukai Shoichiro, Yorita Kenji, Kawagoe Yukari, Katayama Yuichi, Nakahara Kozue, Kamibeppu Toyoharu, Sugie Satoru, Tukino Hiromasa, Kamoto Toshiyuki, Kataoka Hiroaki
Department of Urology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan,
Hum Cell. 2015 Jan;28(1):44-50. doi: 10.1007/s13577-014-0101-3. Epub 2014 Sep 4.
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.
据报道,肾细胞癌(RCC)中MET的高表达以及骨转移中MET的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,我们通过免疫组织化学分析了MET和matriptase(肝细胞生长因子的特异性细胞激活剂)的表达水平。我们获取了17例发生转移的RCC患者的肾切除标本,以及7例在2008年至2012年间在我院接受转移灶切除术的RCC骨转移患者的骨转移标本。我们用抗人MET多克隆抗体和抗人matriptase多克隆抗体检测样本,并比较阳性和阴性组的术后总生存率(OS)。在8/17(47%)的肾切除标本和6/7(86%)的骨标本的原发部位观察到MET高表达。Matriptase在6/17(35%)的肾切除标本和所有7例(100%)的骨标本中表达。有趣的是,在5/7的骨标本的破骨细胞中matriptase强烈表达。MET(-)组的术后OS率显著高于MET(+)组。在骨转移的RCC细胞中观察到的MET和matriptase高表达以及破骨细胞中matriptase的表达表明它们在骨转移中具有重要意义。