山崎 浩司 (ヤマサキ コウジ)

YAMASAKI Koji

写真a

所属

医学部 医学科 発達泌尿生殖医学講座泌尿器科学分野

職名

助教

外部リンク

研究分野 【 表示 / 非表示

  • ライフサイエンス / 泌尿器科学

 

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  • Matriptase-Induced Phosphorylation of MET is Significantly Associated with Poor Prognosis in Invasive Bladder Cancer; an Immunohistochemical Analysis 査読あり

    Yamasaki K., Mukai S., Nagai T., Nakahara K., Fujii M., Terada N., Ohno A., Sato Y., Toda Y., Kataoka H., Kamoto T.

    International journal of molecular sciences   19 ( 12 )   2018年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:International journal of molecular sciences  

    Hepatocyte growth factor (HGF) plays an important role in cancer progression via phosphorylation of MET (c-met proto-oncogene product, receptor of HGF). HGF-zymogen (pro-HGF) must be processed for activation by HGF activators including matriptase, which is a type II transmembrane serine protease and the most efficient activator. The enzymatic activity is tightly regulated by HGF activator inhibitors (HAIs). Dysregulated pro-HGF activation (with upregulated MET phosphorylation) is reported to promote cancer progression in various cancers. We retrospectively analyzed the expression of matriptase, phosphorylated-MET (phospho-MET) and HAI-1 in tumor specimens obtained from patients with invasive bladder cancer by immunohistochemistry. High expression of phospho-MET and increased expression of matriptase were significantly associated with poor prognosis, and high matriptase/low HAI-1 expression showed poorer prognosis. Furthermore, high expression of matriptase tended to correlate with phosphorylation of MET. Increased expression of matriptase may induce the ligand-dependent activation of MET, which leads to poor prognosis in patients with invasive bladder cancer.

    DOI: 10.3390/ijms19123708

    Scopus

    PubMed

  • Dysregulated HAI-2 plays an important role in renal cell carcinoma bone metastasis through ligand-dependent MET phosphorylation 査読あり

    Yamasaki K., Mukai S., Sugie S., Nagai T., Nakahara K., Kamibeppu T., Sakamoto H., Shibasaki N., Terada N., Toda Y., Kataoka H., Kamoto T.

    Cancers   10 ( 6 )   2018年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Cancers  

    © 2018 by the authors. Licensee MDPI, Basel, Switzerland. MET, a c-met proto-oncogene product and hepatocyte growth factor (HGF) receptor, is known to play an important role in cancer progression, including bone metastasis. In a previous study, we reported increased expression of MET and matriptase, a novel activator of HGF, in bone metastasis. In this study, we employed a mouse model of renal cell carcinoma (RCC) bone metastasis to clarify the significance of the HGF/MET signaling axis and the regulator of HGF activator inhibitor type-2 (HAI-2). Luciferase-transfected 786-O cells were injected into the left cardiac ventricle of mice to prepare the mouse model of bone metastasis. The formation of bone metastasis was confirmed by whole-body bioluminescent imaging, and specimens were extracted. Expression of HGF/MET-related molecules was analyzed. Based on the results, we produced HAI-2 stable knockdown 786-O cells, and analyzed invasiveness and motility. Expression of HGF and matriptase was increased in bone metastasis compared with the control, while that of HAI-2 was decreased. Furthermore, we confirmed increased phosphorylation of MET in bone metastasis. The expression of matriptase was upregulated, and both invasiveness and motility were increased significantly by knockdown of HAI-2. The significance of ligand-dependent MET activation in RCC bone metastasis is considered, and HAI-2 may be an important regulator in this system.

    DOI: 10.3390/cancers10060190

    Scopus

    PubMed

  • Caveolin-1 and -2 regulate cell motility in castration-resistant prostate cancer. 査読あり

    Kamibeppu T, Yamasaki K, Nakahara K, Nagai T, Terada N, Tsukino H, Mukai S, Kamoto T

    Research and reports in urology   10   135 - 144   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2147/RRU.S173377

    PubMed

  • Plasma macrophage-stimulating protein and hepatocyte growth factor levels are associated with prostate cancer progression

    Sugie S., Mukai S., Yamasaki K., Kamibeppu T., Tsukino H., Kamoto T.

    Human Cell   29 ( 1 )   22 - 29   2016年1月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Human Cell  

    © 2015, Japan Human Cell Society and Springer Japan. Hepatocyte growth factor (HGF) is a well-known multifunctional growth factor, and evidence has accumulated indicating that the HGF/MET (HGF receptor) signaling axis is involved in the progression of cancer. Macrophage-stimulating protein (MSP) is also known as a growth factor which activates not only macrophages but also cancer cells and osteoclasts through the activation of the specific Receptor d’origine nantais (RON). Pro-HGF and pro-MSP lack biological activity and, therefore, require proteolytic activation for conversion to an active two-chain form by HGF activator (HGFA). Although, there are several studies on HGF/MET signaling with castration-resistant prostate cancer (CRPC) and bone metastasis, reports on plasma protein are rare. In addition, the MSP/RON signaling axis in PC is not well understood. Here, we analyzed associations between PC progression and plasma HGF and MSP levels. We tested plasma samples from 58 patients with PC: 36 with castration-resistant (CR) PC and 22 with pretreatment for PC as control. We used enzyme-linked immunosorbent assay (ELISA) kit to determine plasma levels of HGF, MSP and HGFA, and examined correlations with clinicopathological characteristics such as Gleason grade and bone metastasis. PCR was used to evaluate HGF and MSP-related molecules in PC cell lines. Plasma levels of HGF, MSP and HGFA in the CRPC group were higher than in the control group (HGF: P < 0.001; MSP: P = 0.008; HGFA: P < 0.001). HGF and MSP levels were significantly correlated (P = 0.003). In the CRPC group, plasma HGF and MSP levels and Gleason score were not correlated; however, high plasma MSP level correlated with bone metastasis. (P = 0.016). In cell lines, PC3 expressed significantly more HGF, MET and RON than did LNCaP (P < 0.001), and both cell lines expressed MSP. Plasma concentrations of HGF, MSP and HGFA are significantly elevated in patients with CRPC. Also, as plasma MSP levels are significantly associated with bone metastasis in CRPC patients, MSP may be a candidate for serum marker of bone metastasis. Our results show the importance of the HGF/MET and MSP/RON signaling systems in CRPC.

    DOI: 10.1007/s13577-015-0123-5

    Scopus

    PubMed

  • Significant Association of Caveolin-1 and Caveolin-2 with Prostate Cancer Progression.

    Sugie S, Mukai S, Yamasaki K, Kamibeppu T, Tsukino H, Kamoto T

    Cancer genomics & proteomics   12 ( 6 )   391 - 6   2015年11月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    PubMed

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