Masahiro Nakano

Publications (2)15.71 Total impact

• Article: Tumor cell-derived angiopoietin-like protein ANGPTL2 is a critical driver of metastasis.

  Motoyoshi Endo, Masahiro Nakano, Tsuyoshi Kadomatsu, Shigetomo Fukuhara, Hiroaki Kuroda, Shuji Mikami, Tai Hato, Jun Aoi, Haruki Horiguchi, Keishi Miyata, [......], Tsunekazu Hishima, Hiroaki Nomori, Takaaki Ito, Yutaka Yamamoto, Takashi Minami, Seiji Okada, Takashi Takahashi, Naoki Mochizuki, Hirotaka Iwase, Yuichi Oike
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  ABSTRACT: Strategies to inhibit metastasis have been mainly unsuccessful in part due to insufficient mechanistic understanding. Here, we report evidence of critical role for the angiopoietin-like protein 2 (ANGPTL2) in metastatic progression. In mice, Angptl2 has been implicated in inflammatory carcinogenesis but it has not been studied in human tumors. In patients with lung cancer, elevated levels of ANGPTL2 expression in tumor cells within the primary tumor were associated with a reduction in the period of disease-free survival after surgical resection. Transcription factors NFATc, ATF2, and c-Jun upregulated in aggressive tumor cells promoted increased Angptl2 expression. Most notably, tumor cell-derived ANGPTL2 increased in vitro motility and invasion in an autocrine/paracrine manner, conferring an aggressive metastatic tumor phenotype. In xenograft mouse models, tumor cell-derived ANGPTL2 accelerated metastasis and shortened survival whereas attenuating ANGPTL2 expression in tumor cells-blunted metastasis and extended survival. Overall, our findings showed that tumor cell-derived ANGPTL2 drives metastasis and provided an initial proof of concept for blockade of its action as a strategy to antagonize the metastatic process.
  Cancer Research 02/2012; 72(7):1784-94. · 7.86 Impact Factor
• Article: Angiopoietin-like protein 2 is an important facilitator of inflammatory carcinogenesis and metastasis.

  Jun Aoi, Motoyoshi Endo, Tsuyoshi Kadomatsu, Keishi Miyata, Masahiro Nakano, Haruki Horiguchi, Aki Ogata, Haruki Odagiri, Masato Yano, Kimi Araki, Masatoshi Jinnin, Takaaki Ito, Satoshi Hirakawa, Hironobu Ihn, Yuichi Oike
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  ABSTRACT: Chronic inflammation plays important roles at different stages of cancer development, including carcinogenesis, tumor invasion, and metastasis, but molecular mechanisms linking inflammation to cancer development have not been fully clarified. Here, we report that expression of angiopoietin-like protein 2 (Angptl2), recently identified as a chronic inflammation mediator, is highly correlated with the frequency of carcinogenesis in a chemically induced skin squamous cell carcinoma (SCC) mouse model. Furthermore, Angptl2 expression in SCC is highly correlated with the frequency of tumor cell metastasis to distant secondary organs and lymph nodes. When SCC was induced in transgenic mice expressing Angptl2 in skin epithelial cells, epithelial-to-mesenchymal transitions in SCC as well as tumor angiogenesis and lymphangiogenesis were significantly increased, resulting in increased tumor cell metastasis and shortened survival compared with wild-type mice. Conversely, in a chemically induced SCC mouse model, carcinogenesis and metastasis were markedly attenuated in Angptl2 knockout mice, resulting in extended survival compared with wild-type mice. Overall, we propose that Angptl2 contributes to increased carcinogenesis and metastasis and represents a novel target to antagonize these pathologies.
  Cancer Research 12/2011; 71(24):7502-12. · 7.86 Impact Factor