Sato

 

教授 医博 佐藤 靖史
助教 理博 鈴木 康弘
助教 理博 小林 美穂
博士研究員 医博 イ ウンソ



研究プロジェクト

血管新生の分子制御に関する研究本研究は、血管内皮細胞のバイオロジーに関する基盤的研究と、その知見を基にしたトランスレーショナル研究の推進を目指ている。 我々は、血管新生の中心的な促進因子VEGFの刺激によって血管内皮細胞で発現誘導される遺伝子群の中から血管新生のnegative feedback 調節因子としての機能を果たすと考えられる新規血管新 生抑制因子Vasohibin-1(VASH-1)とそのホモログVasohibin-2(VASH-2)を単離・同定した。VASH-1は血管新生のみならずリンパ管新生に対して広いスペクトルムで抑制活性を有しており、このような活性を持つ内因性因子はVASH-1が初めてのものである。特に、癌の発育と遠隔転移は血管新生に、リンパ管新生はリンパ節転移に直結することから、VASH-1の癌治療への応用を目指している。これに対してVASH-2は、VASH-1と拮抗して血管新生を促進する因子である。血管新生モデルでの観察では、VASH-1は主に発芽領域よりも後方の血管内皮細胞に発現して血管新生を終息させるのに対し、VASH-2は、主に血管新生が活発な発芽領域に浸潤している骨髄由来CD11b陽性の単核球に発現して、発芽部位の血管新生を促進することが分かった。ところが、癌組織においては間質に浸潤する単核球のみならず癌細胞もVASH-2を発現し、腫瘍血管新生を介して癌の発育を促進するばかりか、がん細胞自身に作用してがん幹細胞としての特性獲得に関与する可能性のあること観察している。以上より、VASH-1の作用を増強するのみならず、VASH-2の作用を阻害することがより効果的な治療法となると考え、今後開発研究を進める。

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発表論文

1995
Sato, Y. Activation of latent TGF- at the vascular wall. Roles of endothelial cells and mural pericytes or smooth muscle cells. J. Atheroscler. Thromb.2:24-29, 1995.

Hori, K., Zhang, Q.H., Li, H.C., and Saito, S. Variation of growth rate of a rat tumour during a light-dark cycle: correlation with circadian fluctuations in tumour blood flow. Br. J. Cancer. 71:1163-1168, 1995.

1996
Hori, K., Zhang, Q.-H., Li, H.-C., Saito, S., and Sato, Y. Timing of cancer chemotherapy based on circadian variation in tumor blood flow. Int. J. Cancer 65:360-364, 1996.

Ono, M., Kawahara, N., Goto, D., Wakabayashi, Y., Ushiro, S., Yoshida, S., Izumi, H., Kuwana, M., and Sato, Y. Inhibition of tumor growth and neovascularization by an anti-gastric ulcer agent, irsogladine. Cancer Res. 56:1512-1516, 1996.

Abe, H., Abe, M., Tanaka, K., Iwasaka, C., and Sato, Y. Simultaneous bindings of uPA and latnt TGF- for the activation of latent TGF-in homotypic smooth muscle cells. Tohoku J. Exp. Med. 179:23-34, 1996.

Ono, M., Izumi, H., Yoshida, S., Goto, D., Jimi, S., Kawahara, N., Shono, T., Ushiro, S., Ryuto, M., Kohno, K., Sato, Y., and Kuwano, M. Angiogenesis as a new target for cancer treatment. Cancer Chemother. Pharmacol. 38 (Suppl.):S78-S82, 1996.

Hori, K., Saito, S., and Sato, Y. Daily changes in tumor blood flow after cancer chemotherapy. Microcirculation Annual 1996:215-216, 1996.

Iwasaka, C., Tanaka, K., Abe, M., and Sato, Y. Ets-1 regulates angiogenesis by inducing the expression of urokinase-type plasminogen activator and matrix metalloproteinase-1 and the migration of vascular endothelial cells. J. Cell. Physiol. 169:522-531, 1996.

1997
Hori, K., Li, H.-C., Saito, S., and Sato, Y. Increased growth and incidence of lymph node metastases due to the angiogenesis inhibitor AGM-1470. Br. J. Cancer 75:1730-1734, 1997.

Sato, Y., Iwasaka, C., Tanaka, K., Okinawa M., Oda, N., Igarashi, T., Nakano, M., Abe, M. Regulation of angiogenesis. in “Development of antimetastatic & antiangiogenic drugs” pp. 148-158, 1997.

1998
Abe, M., Oda, N., and Sato, Y. Cell-associated activation of latent transforming growth factor- by calpain. J. Cell. Physiol. 174:186-193, 1998.

Takahashi, H., Abe, M., Sugawara, T., Tanaka, K., Saito, Y., Fujimura, S., Shibuya, M., and Sato, Y. Clotrimazole, an imidazole antimycotic, is a potent inhibitor of angiogenesis. Jpn. J. Cancer, Res. 89:445-451, 1998.

Tanaka, K., Oda, N., Iwasaka, C., Abe, M., and Sato, Y. Induction of Ets-1 in endothelial cells during re-endothelialization after denuding injury. J. Cell. Physiol. 176:235-244, 1998.

Sato, Y. Role of a transcription factor ETS-1 in angiogenesis. Connective Tissue 30:291-295, 1998.

Sato, Y. Transcription factor ETS-1 as a molecular target for angiogenesis inhibition. Human Cell 11:207-214, 1998.

1999
Oda, N., Abe, M., and Sato, Y. ETS-1 converts endothelial cells to the angiogenic phenotype by inducing the expression of matrix metalloproteinases and integrin 3. J. Cell. Physiol. 178:121-132, 1999.

Okamoto, O., Fujiwara, S., Abe, M., and Sato, Y. Dermatopontin interacts with transforming growth factor  and enhances its biological activity. Biochem. J. 337:537-541, 1999.

Nishimura, M., Miki, T., Yashima, R., Sato, Y., and Seino S. Angiopoietin-3, a novel member of the angiopoietin family. FEBS Lett. 448:254-256, 1999.

Kanno, S., Oda, N., Abe, M., Saito, S., Hori, K., Handa, Y., Tabayashi, K., and Sato, Y. Establishment of a simple and practical procedure applicable to therapeutic angiogenesis. Circulation 99:2682-2687, 1999.

Tanaka, K., Abe, M., and Sato, Y. Roles of ERK1/2 and p38 MAP kinase in the signal transduction of bFGF in endothelial cells during angiogenesis. Jpn. J. Cancer Res. 90:647-654, 1999.

Nihei, Y., Suga, Y., Morinaga, Y., Ohishi, K., Okano, A., Ohsumi, K., Hatanaka, T., Nakagawa, R., Tsuji, T., Akiyama, Y., Saito, S., Hori, K., Sato, Y., and Tsuruo, T. A Novel Combretastatin A-4 derivative, AC-7700, shows marked antitumor activity against advanced solid tumors and orthotopically transplanted tumors. Jpn. J. Cancer Res. 90: 1016-1025, 1999.

Hori, K., Saito, S., Nihei, Y., Suzuki, M., and Sato, Y. Antitumor effects due to irreversible stoppage of tumor tissue blood flow: evaluation of a novel combretastatin A-4 derivative, AC7700. Jpn. J. Cancer Res. 90:1026-1038, 1999.

Nihei, Y., Suzuki, M., Okano, A., Tsuji, T., Akiyama, Y., Tsuruo, T., Saito, S., Hori, K., and Sato, Y. Evaluation of antivascular and antimitoitic effects of tubulin binding agents to solid tumor therapy. Jpn. J. Cancer Res. 90:1387-1396, 1999.

Kubota, K., Tada, M., Yamada, S., Hori, K., Saito, S., Iwata, R., Sato, K., Fukuda, H., and Ido, T. Comparison of the distribution of fluorine-18 fluoromisonidazole, deoxyglucose and methionine in tumour tissue. Eur. J. Nucl. Med. 26:750-757, 1999.

Yamamoto, H., Atsuchi, N., Tanaka, H., Ogawa, W., Abe, M., Takeshita, A., and Ueno, H. Separate roles for H-Ras and Rac in signaling by transforming growth factor (TGF)-. H-Ras is essential for activation of MAP kinase, partially required for transcriptional activation by TGF-, but not required for signaling of growth suppression by TGF-. Eur. J. Biochem. 264:110-119, 1999.

2000
Namba, K., Abe, M., Saito, S., Satake, M., Ohmoto, T., Watanabe, T, and Sato, Y. Indispensable role of the transcription factor PEBP2/CBF in angiogenic activity of a murine endothelial cell MSS31. Oncogene 19:173-179, 2000.

Hori, K., Saito, S., Takahashi, H., Sato, H., Maeda, H., Sato, Y. Tumor-selective blood flow decrease induced by an angiotensin converting enzyme inhibitor, temocapril hydrochloride. Jpn. J. Cancer Res. 91: 261-269, 2000.

Sato, Y. Molecular mechanism of angiogenesis: Role of Ets-1 in angiogenesis. in “New Frontier in Vascular Biology; Thrombosis and hemostasis” Eibun Press, Ltd. pp.1-6, 2000.

Tanaka, M., Narumi, K., Isemura, M., Abe, M., Sato, Y., Abe, T., Saijo, Y., Nukiwa, T., and Satoh, K. Expression of the 37-kDa laminin binding protein in murine lung tumor cell correlates with tumor angiogenesis. Cancer Lett. 153:161-168, 2000.

Kanno, S., Oda, N., Abe. M., Terai, Y., Ito, M., Shitara, K., Tabayashi, K., Shibuya, M., and Sato, Y. Roles of two VEGF receptors, Flt-1 and KDR, in the signal transduction of VEGF effects in human vascular endothelial cells. Oncogene 19:2138-2146, 2000.

Sato, Y., Kanno, S., Oda, N., Abe. M., Ito, M., Shitara, K., and Shibuya, M. Properties of two VEGF receptors, Flt-1 and KDR, in the signal transduction. Ann. N. Y. Acad. Sci. 901:201-207, 2000.

Nakano, T., Abe, M., Tanaka, K., Shineha, R., Satomi, S., and Sato, Y. Angiogenesis Inhibition by Transdominant Mutant Ets-1. J. Cell. Physiol. 184:255-262, 2000.

Sato, Y. Molecular mechanism of angiogenesis: transcription factors and their therapeutic relevance. Pharmacol. Ther. 87:51-60, 2000.

Sato, Y., Abe, M., Tanaka, K., Iwasaka , C., Oda, N., Kanno, S., Oikawa, M., Nakano, T., and Igarashi T. Signal transduction and transcriptional regulation of angiogenesis. Adv. Exp. Med. Biol. 476:109-115, 2000.

2001
Sato Y. Role of ETS family transcription factors in vascular development and angiogenesis. Cell Struct. Funct. 26: 19-24, 2001.

Yashima, R., Abe, M., Tanaka, K., Ueno, H., Shitara, K., Takenoshita, S., and Sato, Y Heterogeneity of the signal transduction pathways for VEGF-induced MAPKs activation in human vascular endothelial cells. J. Cell. Physiol. 188:201-210, 2001.

Teruyama, K., Abe, M., Iwasaka-Yagi, C. Nakano, T., Takahashi, S., Yamada, S., and Sato, Y. Role of transcription factor Ets-1 in the apoptosis of human vascular endothelial cells. J. Cell. Physiol. 188:243-252, 2001.

Iwasaka-Yagi, C., Abe, M., and Sato, Y. TGF- attenuates the transactivation activity of Ets-1 despite its induction via the inhibition of DNA binding. Tohoku J. Exp. Med. 193: 311-318, 2001.

Terai, Y., Abe, M., Miyamoto, K., Koike, M., Yamasaki, M., Ueda, M., Ueki, M., Sato, Y. Vascular smooth muscle cell growth-promoting factor/F-spondin inhibits angiogenesis via the blockade of integrin v3 on vascular endothelial cells. J. Cell. Physiol. 88:394-402, 2001.

Igarashi, T., Abe, M., Oikawa, M., Nukiwa, T., and Sato, Y. Retinoic Acids Repress the Expression of ETS-1. Tohoku J. Exp. Med. 194: 35-43, 2001.

Teruyama, K., Abe, M., Nakano, T., Takahashi, S., Yamada, S., and Sato, Y. Neuropilin-1 is a downstream target of transcription factor Ets-1 in human umbilical vein endothelial cells. FEBS Lett. 504: 1-4, 2001.

Oikawa, M., Abe, M., Kurosawa, H., Hida, W., Shirato, K., and Sato, Y. Hypoxia induces transcription factor ETS-1 via the activity of hypoxia inducible factor-1. Biochem. Biophys. Res. Commun. 289:39-43, 2001.

Sato, Y., Teruyama, K., Nakano, T., Oda, N., Abe, M., Tanaka, K., and Iwasaka-Yagi, C. Role of transcription factors in angiogenesis: Ets-1 promotes angiogenesis as well as endothelial apoptosis. Ann. N. Y. Acad. Sci. 947, 117-123, 2001.

Abe, M., and Sato, Y. cDNA microarray analysis of the gene expression profile of VEGF-induced human umbilical vein endothelial cells. Angiogenesis 4: 289-298, 2001.

Hori, K., Saito, S., Sato, Y., Kubota, K. Stoppage of blood flow in 3-methyl- cholanthrene-induced autochthonous primary tumor due to a novel combretastatin A-4 derivative, AC7700, and its antitumor effect. Med. Sci. Monit. 7: 26-33, 2001.

2002
Abe, M., Inoue, D., Matsunaga, K., Ohizumi, Y., Ueda, H., Asano, T., Murakami, M., and Sato, Y. Goniodomin A, an antifungal polyether macrolide, exhibits antiangiogenic activities via inhibiting actin reorganization of endothelial cells. J. Cell. Physiol. 190: 109-116, 2002.

Miyashita, H., Yamazaki, T., Akada, T., Niizeki, O., Ogawa, M., Nishikawa, S-I., and Sato, Y. A mouse orthologue of puromycin insensitive leucyl-specific aminopeptidase (PILSAP) is expressed in endothelial cells and plays an important role in angiogenesis. Blood 99: 3241-3249, 2002.

Abe, M., Oda, N., Shibata, K., Yamasaki, M., and Sato, Y. Augmented binding and activation of latent transforming growth factor- by a tryptic fragment of latency associated peptide. Endothelium 9: 25-36, 2002.

Akada, K, Yamazaki, T., Miyashita, H., Niizeki, O., Abe, M., Sato, A., Satomi, S., and Sato, Y. Puromycin insensitive leucyl-specific aminopeptidase (PILSAP) is involved in the activation of endothelial integrins. J. Cell. Physiol. 193: 253-262, 2002.

Hori K, Saito S, Kubota K. A novel combretastatin A-4 derivative, AC7700, strongly stanches tumour blood flow and inhibits growth of tumours developing in various tissues and organs. Br. J. Cancer. 86:1604-1614, 2002.

2003
Sato, Y. The ETS family of transcription factors. In “Genetics of Angiogenesis” (BIOS Scientific Publisher Ltd. Oxford) pp. 55-68, 2003.

Nakagawa, T., Abe, M., Yamazaki, T., Miyashita, H., Niwa, H., Kokubun S., and Sato, Y. HEX acts as a negative regulator of angiogenesis by modulating the expression of angiogenesis-related gene in endothelial cells in vitro. Arterioscler. Thromb. Vasc. Biol. 23: 231-237, 2003.

Hori, K., Saito, S., Sato, Y., Akita, H., Kawaguchi, T., Sugiyama, K., and Sato, H. Differential relationship between changes in tumour size and microcirculatory functions induced by therapy with an antivascular drug and with cytotoxic drugs: implications for evalustion of therapeutic efficacy ofAC7700 (AVE8062). Eur. J. Cancer. 39: 1957-1966, 2003.

Sato, Y. Neovascularization; its molecular mechanism and biology. Intern. Med. 42:295-297, 2003.

Sato, Y. Molecular diagnosis of tunmor angiogenesis and anti-angiogenic cancer therapy. Int. J. Clin. Oncol. 8:200-206, 2003.

Sato, Y. Aminopeptidase and angiogenesis. Endothelium 10: 287-290, 2003.

Hori, K., Saito, S. Microvascular mechanisms by which the combretastatin A-4 derivative AC7700 (AVE8062) induces tumour blood flow stasis. Br. J. Cancer 89:1334-1344, 2003.

2004
Hori, K., Saito, S. Induction of tumour blood flow stasis and necrosis a new function for epinephrine similar to that of combretastatin A-4 derivative AVE8062 (AC7700). Br. J. Cancer 90:549-553, 2004.

Hasegawa, Y., Abe, M., Shiiba, K., Sasaki, I, and Sato, Y. Transcriptional regulation of humen angiopoietin-2 by transcription factor ETS-1. Biochem. Biophys. Res. Commun. 361: 52-58, 2004.

Niizeki, O., Miyashita, H., Yamasaki, T., Akada, T., Abe, M., Yoshida, N., Toshio Watanabe, Yoshimatsu, H., and Sato, Y. Transcriptional regulation of angiogenesis-related puromycin-insensitive leucyl-specific aminopeptidase in endothelial cells. Arch. Biochem. Biophys. 424: 63-71, 2004.

Watanabe, D., Takagi, H., Suzuma, K., Suzuma, I., Oh, H., Ohashi, H., Kemmochi, S., Uemura, A., Ojima, T., Suganami, E., Miyamoto, N., Sato, Y., and Honda, T. Transcription Factor Ets-1 Mediates Ischemia- and VEGF-dependent Retinal Neovascularization. Am. J. Pathol. 164: 1827-1835, 2004.

Miyashita, H., Kanemura, M., Yamazaki, T., Abe, M., and Sato, Y. Vascular endothelial zinc finger 1 (Vezf1), an endothelium-specific transcription factor, plays an important role in angiogenesis: possible contribution of stathmin/OP18 as a downstream target gene. Arterioscler. Thromb. Vasc. Biol. 24: 878-884, 2004.

Sato, Y. Role of aminopeptidase in angiogenesis. Biol. Pharm. Bull. 27: 772-776, 2004.

Hashiya, N., Jo, N., Aoki, M., Matsumoto, K., Nakamura, T., Sato, Y., Ogata, N., Ogihara, T., Kaneda, Y., Morishita, R. In vivo evidence of angiogenesis induced by transcription factor Ets-1. Ets-1 is located upstream of angiogenesis cascade. Circulation 109:3035-3041, 2004.

Iizuka, M., Abe, M., Shiiba, K., Sasaki, I, and Sato, Y. Down syndrome candidate region 1 (DSCR1), a downstream target of VEGF in endothelial cells, regulates cell migration and angiogenesis via the functional interaction with integrin v3. J. Vasc. Res. 41:334-344, 2004.

Yamazaki, T., Akada, T., Niizeki, O., Suzuki, T., Miyashita, H., and Sato, Y. Puromycin insensitive leucyl-specific aminopeptidase (PILSAP) binds and catalyses PDK1, allowing VEGF-stimulated activation of S6K for endothelial cell proliferation and angiogenesis. Blood 104:2345-2352, 2004.

Watanabe, K., Hasegawa Y., Yamashita, H., Shimizu, K., Ding, Y., Abe, M., Ohta, H., Imakawa, K., Hojo, K., Maki, H., Sonoda, H., and Sato, Y. Vasohibin as an endothelium-derived negative feedback regulator of angiogenesis. J. Clin. Invest. 114: 884-886, 2004.

Tanaka, H., Terada, Y., Kobayashi, T., Okado, T., Inoshita, S., Kuwahara, M., Seth, A., Sato, Y., and Sasaki, S. Expression and function of Ets-1 during experimental acute renal failure in rats. J. Am. Soc. Nephrol. 15:3083-3092, 2004.

Hori, K., Saito, S., and Tamai, M. Effect of irradiation on neovascularization in rat skinfold chambers: Implications for clinical trials of low-dose radiotherapy for wet-type age-related macular degeneration. Int. J. Radiat. Oncol. Biol. Phys. 60:1564-1571, 2004.

Kanemura, M., Abe, M., Ueda, M., Ueki, M., Awaya, A., and Sato, Y. MS-818 accelerates mobilization of endothelial progenitor cells and differentiation to endothelial cells. Endothelium 11: 221-230, 2004.

2005
Shimizu, K., Watanabe, K., Yamashita, H., Abe, M., Yoshimatsu, H., Ohta, H., Sonoda, H., and
Sato, Y. Gene regulation of a novel angiogenesis inhibitor, vasohibin, in endothelial cells. Biochem. Biophys. Res. Commun. 327: 700-7006, 2005.

Sato, Y. Angiogenesis and its relevance to tumor biology. In “Recent Research Advances in
Cancer” (Research Signpost) pp. 13-21, 2005.

Cho, Y.-J., Abe, M., Kim, S. Y., and Sato, Y. Raf-1 is a binding partner of DSCR1. Arch. Biochem. Biophys. 439: 121-128, 2005.

Miyashita, H., and Sato, Y. Metallothionein1 is a downstream target of VEZF1 in endothelial cells and participates in the regulation of angiogenesis. Endothelium 12: 163-170, 2005.

Hori, K. Antineoplastic strategy: irreversible tumor blood flow stasis induced by the combretastatin A-4 derivative AVE8062 (AC7700). Chemotherapy 51: 357-360, 2005.

2006
Shen, JK., Yang, XR., Sato, Y., and Campochiaro, PA. Vasohibin is Up-regulated by VEGF in the Retina and Suppresses VEGF receptor 2 and Retinal Neovascularization. FASEB J. 20: 723-725, 2006.

Shibuya, T., Watanabe, K., Yamashita, H., Shimizu, K., Miyashita, H., Abe, M., Moriya, T., Ohta, H., Sonoda, H., Shimosegawa, T., Tabayashi, K., and Sato, Y. Isolation of vasohibin-2 as a sole homologue of VEGF-inducible endothelium-derived angiogenesis inhibitor vasohibin: a comparative study on their expressions. Arterioscler. Thromb. Vasc. Biol. 26: 1051-1057, 2006.

Sonoda, H., Ohta, H., Watanabe, K., Yamashita, H., Kimura H., and Sato, Y. Multiple processing forms and their biological activities of a novel angiogenesis inhibitor vasohibin. Biochem. Biophys. Res. Commun. 342: 640-646, 2006.

Sato Y.: Update on endogenous inhibitors of angiogenesis. Endothelium 13: 147-155, 2006.

Yamashita, H., Abe, M., Watanabe, K., Shimizu, K., Moriya, T., Sato, A., Satomi, S., Ohta, H., Sonoda, H., and Sato, Y. Vasohibin prevents arterial neointimal formation through angiogenesis inhibition. Biochem. Biophys. Res. Commun. 345: 919-925, 2006.

Koizumi, T., Abe, M., Yamakuni, T., Ohizumi, Y., Hitotsuyanagi, Y., Takeya, K., and Sato, Y. Metronomic scheduling of a cyclic hexapeptide RA-VII for anti-angiogenesis, tumor vessel maturation, and anti-tumor activity. Cancer Sci. 97: 665-674, 2006.

Abe M., and Sato, Y. Puromycin insensitive leucyl-specific aminopeptidase (PILSAP) is required for the development of vascular as well as hematopoietic system in embryoid bodies. Genes Cells 11:719-729, 2006.

Mizui, M., Isaka, Y., Takabatake, Y., Sato, Y., Kawachi, H., Shimizu, F., Takahara, S., Ito, T., and Imai, E. Transcription factor ets-1 is essential for mesangial matrix remodeling. Kidney Int. 70: 298-305, 2006.

Nagasaka, M., Kohzuki, M., Fujii, T., Kanno, S., Kawamura, T., Onodera, H., Itoyama, Y., Ichie, M., Sato, Y. Effect of low-voltage electrical stimulation on angiogenic growth factors in ischaemic rat skeletal muscle. Clin. Exp. Pharmacol. Physiol. .33: 623-627, 2006.

Sato, Y. An endothelium-derived angiogenesis inhibitor vasohibin and its significance in tumor angiogenesis. Cancer Chemother. Pharmacol. Suppl 7: 69-72, 2006.

Kim, Y.S., Lee, H.J., Cho, K.O., Kim, S.Y., Sato, Y., and Cho, Y.J. Down Syndrome Candidate Region 1 increases protein stability of IκBα: Implication for its anti-inflammatory effects. J. Biol. Chem. 281: 39051-39061, 2006.

Candi E, Terrinoni A, Rufini A, Chikh A, Lena AM, Suzuki Y, Sayan BS, Knight RA, Melino G. p63 is upstream of IKK alpha in epidermal development. J. Cell Sci. 119: 4617-4622 ,2006.

Kobayashi M, Nishita M, Mishima T, Ohashi K, Mizuno K. MAPKAPK-2-mediated LIM-kinase activation is critical for VEGF-induced actin remodeling and cell migration. EMBO J. 25: 713-726, 2006.

2007
Sato, Y., and Sonoda, H. The vasohibin family: a negative regulatory system of angiogenesis genetically programmed in endothelial cells. Arterioscler. Thromb. Vasc. Biol. 27: 37-41, 2007.

Saito, A., Sugawara, A., Uruno, A., Kudo, M., Kagechika, H., Sato, Y., Owada, Y., Kondo, H., Sato, M., Kurabayashi, M., Imaizumi, M., Tsuchiya, S., and Ito, S. All-trans retinoic acid induces in vitro angiogenesis via retinoic acid receptor: Possible involvement of paracrine effects of endogenous vascular endothelial growth factor signaling. Endocrinology 148: 1412-1423, 2007.

Suzuki, T., Abe, M., Miyashita, H., Kobayashi, T., and Sato, Y. Puromycin insensitive leucyl-specific aminopeptidase (PILSAP) affects RhoA activation in endothelial cells. J. Cell. Physiol. 211: 708-715, 2007.

Sato, Y. Endogenous inhibitors of angiogenesis. Angiogenesis. In “Basic Science and Clinical Applications” (Transworld Research Network) pp 1-14, 2007.

2008
Sato, Y. VEGFR1 for lymphangiogenesis: an alternative signaling pathway? Arterioscler. Thromb. Vasc. Biol. 28: 604-605, 2008.

Yoshinaga, K., Moriya, T., Nagase, S., Takano, T., Niikura, H., Ito, K., Nobuo Yaegashi, N., and Sato, Y. Vasohibin, a novel endothelium-derived angiogenesis inhibitor: its expression on endometrial carcinoma in relation to tumor vascularity. Cancer Sci. 99: 914-919, 2008.

Wakusawa, R., Abe, T., Sato, H., Yoshida, M., Kunitaka, H., Sato, Y., and Nishida K. Expression of vasohibin, an antiangiogenic factor, in human choroidal neovascular membranes. Am. J. Ophthalmol. 146:235-243, 2008.

Hori, K., Furumoto, S., and Kubota, K. Tumor blood flow interruption after radiotherapy strongly inhibits tumor regrowth. Cancer Sci. 99:1485-1491, 2008.

2009
Tamaki K, Moriya T, Sato Y, Ishida T, Maruo Y, Yoshinaga K, Ohuchi N, Sasano H. Vasohibin-1 in human breast carcinoma: a potential negative feedback regulator of angiogenesis. Cancer Sci. 100:88-94, 2009.

Lefter LP, Dima S, Sunamura M, Furukawa T, Sato Y, Abe M, Chivu M, Popescu I, and Horii A. Transcriptional silencing of ETS-1 efficiently suppresses angiogenesis of pancreatic cancer. Cancer Gene Ther. 16:137-148, 2009.

Sato H, Abe T, Wakusawa R, Asai N, Kunikata H, Ohta H, Sonoda H, Sato Y, and Nishida K. Vitreous levels of vasohibin-1 and vascular endothelial growth factor in patients with proliferative diabetic retinopathy. Diabetologia. 52:359-361, 2009.

Nishida Y, Shibata K, Yamasaki M, Sato Y, and Abe M. A possible role of vimentin on the cell surface for the activation of latent transforming growth factor-. FEBS Lett. 583: 308–312, 2009.

Naito H, Kidoya H, Sato Y, and Takakura N. Induction and expression of anti-angiogenic vasohibins in the hematopoietic stem/progenitor cell population. J. Biochem. 145: 653-659, 2009.

Kimura H, Miyashita H, Suzuki Y, Kobayashi M, Watanabe K, Sonoda H, Ohta H, Fujiwara T, Shimosegawa T and Sato Y. Distinctive localization and opposed roles of vasohibin-1 and vasohibin-2 in the regulation of angiogenesis. Blood 113: 4810-4818, 2009.

Hosaka T, Kimura H, Heishi T, Suzuki Y, Miyashita H, Ohta H, Sonoda H, Moriya T, Suzuki S, Kondo T, Sato Y. Vasohibin-1 expressed in endothelium of tumor vessels regulates angiogenesis. Am. J. Pathol. 175: 430-439, 2009.

Taniguchi K, Sasaki K, Watari K, Yasukawa H, Imaizumi T, Ayada T, Okamoto F, Ishizaki T, Kato R, Kohno R, Kimura H, Sato Y, Ono M, Yonemitsu Y, Yoshimura A. Suppression of Sproutys has a therapeutic effect for a mouse model of ischemia by enhancing angiogenesis. PLoS ONE. 4:e5467, 2009.

Nasu T, Maeshima Y, Kinomura M, Hirokoshi-Kawahara K, Tanabe K, Sugiyama H, Sonoda H, Sato Y, Makino H. Vasohibin-1, a negative feedback regulator of angiogenesis, ameliorates renal alterations in a mouse model of diabetic nephropathy. Diabetes 58: 2365-2375, 2009.

Lee HJ, Kim YS, Sato Y, Cho Y-J. RCAN1-4 knockdown attenuates cell growth through the inhibition of Ras signaling. FEBS Lett. 583: 2557-64, 2009.

Suzuki H, Ohkuchi A, Matsubara S, Takei Y, Murakami M, Shibuya M, Suzuki M, Sato Y. The effect of recombinant PlGF-2 on hypertension induced by full-length mouse sFlt-1 adenoviral vector in pregnant mice. Hypertension 54: 1129-1135, 2009.

Miyake K, Nishida K, Kadota Y, Yamasaki H, Nasu T, Saitou D, Tanabe K, Sonoda H, Sato Y, Maeshima Y, Makino H. Inflammatory Cytokine-induced Expression of Vasohibin-1 by Rheumatoid Synovial Fibroblasts. Acta Med. Okayama 63: 349-358, 2009.

Sato, Y. Delta-like 4 and vasohibin 1: two endothelium-produced negative regulators of angiogenesis with distinctive roles. Eur. Cytokine Netw. 20, 1-5, 2009.

2010
Komi Y, Sogabe Y, Ishibashi N, Sato Y, Moriwaki H, Shimokado K, Kojima S. Acyclic retinoid inhibits angiogenesis via suppressing MAPK pathway. Lab. Invest. 90: 52-60, 2010.

Miura S, Mitsui K, Heishi T, Shukunami C, Sekiguchi K, Kondo J, Sato Y, Hiraki Y. Impairment of VEGF-A-stimulated lamellipodial extensions and motility of vascular endothelial cells by Chondromodulin-I, a cartilage-derived angiogenesis inhibitor. Exp. Cell Res. 316: 775-788 2010.

Sato, Y. The vasohibin family. Pharmaceuticals 3, 433-440, 2010.

Heishi T, Hosaka T, Suzuki Y, Miyashita H, Oike Y, Takahashi T, Nakamura T, Arioka S, Mitsuda Y, Takakura T, Hojo K, Matsumoto M, Yamauchi C, Ohta H, Sonoda H, Sato Y. Endogenous angiogenesis inhibitor vasohibin1 exhibits a broad-spectrum anti-lymphangiogenic activity and suppresses lymph node metastasis. Am. J. Pathol. 176: 1950-1958, 2010.

Tamaki K, Sasano H, Maruo Y, Takahashi Y, Miyashita M, Moriya T, Sato Y, Hirakawa H, Tamaki N, Watanabe M, Ishida T, Ohuchi N. Vasohibin-1 as a potential predictor of aggressive behavior of ductal carcinoma in situ of the breast. Cancer Sci. 101: 1051-1058, 2010.

Yoshida T, Sato Y, Morita I, Abe M. Pigpen, a nuclear coiled body component protein is involved in angiogenesis. Cancer Sci. 101: 1170-1176, 2010.

Hori K, Nishihara M, Shiraishi K, Yokoyama M. The combretastatin derivative (Cderiv), a vascular disrupting agent, enables polymeric nanomicelles to accumulate in microtumors. J. Pharm. Sci. 99, 2914-2925, 2010.

ZhouS-Y, Xie Z-I, Xiao O, Yang X-R, Heng BC, Sato, Y. Inhibition of mouse alkali burn induced-corneal neovascularization by recombinant adenovirus encoding human vasohibin-1. Mol. Vision 16: 1389-1398, 2010.

Suzuki Y, Kobayashi M, Miyashita H, Ohta H, Sonoda H, Sato Y. Isolation of a small vasohibin-binding protein (SVBP) and its role in vasohibin secretion. J. Cell Sci. 123: 3094-4101, 2010.

Bai X, Margariti A, Hu Y, Sato Y, Zeng L, Ivetic A, Habi O, Mason JC, Wang X, Xu Q. PKC-deficiency accelerates neointimal lesion of mouse injured artery involving delayed reendothelialization and vasohibin-1 accumulation. Arterioscler. Thromb. Vasc. Biol. 30, 2467-2474, 2010.

2011
Yoshinaga K, Ito K, Moriya T, Nagase S, Takano T, Niikura H, Sasano H, Yaegashi N, Sato Y. Roles of intrinsic angiogenesis inhibitor, vasohibin, in cervical carcinomas. Cancer Sci. 102, 446-51. 2011.

Saito D, Maeshima Y, Nasu T, Yamasaki H, Tanabe K, Sugiyama H, Sonoda H, Sato Y, Makino H. Amelioration of renal alterations in obese type 2 diabetic mice by vasohibin-1, a negative feedback regulator of angiogenesis. Am. J. Phys – Renal Physiol. 300, F873-886, 2011.

Wakusawa R, Abe T, Sato H, Sonoda H, Sato M, Mitsuda Y, Takakura T, Fukushima T, Onami H, Nagai N, Ishikawa Y, Nishida K, Sato Y. Suppression of Choroidal Neovascularization by Vasohibin-1, Vascular Endothelium-derived Angiogenic Inhibitor. Invest Ophthalmol Vis Sci. 52, 3272-3280, 2011.

Miyashita H, Suzuki H, Ohkuchi A, Sato Y. Mutual Balance between Vasohibin-1 and Soluble VEGFR-1 in Endothelial Cells. Pharmaceuticals 4, 1551-1577, 2011.

Sato, Y. Is vasohibin-1 for more than angiogenesis inhibition? J. Biochem. 149, 229-230, 2011.

Sato Y. Persistent vascular normalization as an alternative goal of anti-angiogenic cancer therapy. Cancer Sci. 102, 1253-1256, 2011.

2012
Onami H, Nagai N, Machida S, Kumasaka N, Wakusawa R, Ishikawa Y, Sonoda H, Sato Y, Abe T. Reduction od laser-induced choroidal neovascularization by intravitreal vasohibin-1in monkey eyes. Retina 36, 1204-1213, 2012.

Watanabe T, Okada Y, Hoshikawa Y, Eba S, Notsuda H, Watanabe Y, Ohishi H, Sato Y, Kondo T. A Potent Anti-angiogenic Factor, Vasohibin-1, Ameliorates Experimental Bronchiolitis Obliterans. Transplant Proc. 44: 1155-1157, 2012.

Miyazaki Y, Kosaka T, Mikami S, Kikuchi E, Tanaka N, Maeda T, Ishida M, Miyajima A, Nakagawa K, Okada Y, Sato Y, Oya M. The prognostic significance of vasohibin-1 expression in patients with upper urinary tract urothelial carcinoma. Clin Cancer Res. 18, 4145-4153, 2012.

Takahashi Y, Koyanagi T, Suzuki Y, Saga Y, Kanomata N, Moriya T, Suzuki M, Sato Y. Vasohibin-2 expressed in human serous ovarian adenocarcinoma accelerates tumor growth by promoting angiogenesis. Mol. Cancer Res. 10, 1135-1146, 2012.

Miyashita H, Watanabe T, Hayashi H, Suzuki Y, Nakamura T, Ito S, Ono M, Hoshikawa Y, Okada Y, Kondo T, Sato Y. Angiogenesis inhibitor vasohibin-1 enhances stress resistance of endothelial cells via induction of SOD2 and SIRT1. PLoS One 7, e46459, 2012.

Sato Y. The Vasohibin Family: Novel Regulators of Angiogenesis. Vascul Pharmacol 56, 262-266, 2012.

Ishikawa Y, Nagai N, Onami H, Kumasaka N, Wakusawa R, Sonoda H, Sato Y, Abe T. Vasohibin-1 and retinal pigment epithelium. Adv Exp Med Biol. 723, 305-310, 2012.

2013
Xue X, Gao W, Sun B, Xu Y, Han B, Wang F, Zhang Y, Sun J, Wei J, Lu Z, Zhu Y, Sato Y, Sekido Y, Miao Y, Kondo Y. Vasohibin 2 is transcriptionally activated and promotes angiogenesis in hepatocellular carcinoma. Oncogene. 32, 1724-1734, 2013.

Koyanagi T, Saga Y, Takahashi Y, Suzuki Y, Suzuki M, Sato Y. Downregulation of vasohibin-2, a novel angiogenesis regulator, suppresses tumor growth by inhibiting angiogenesis in endometrial cancer cells. Oncol Lett. 5, 1058-1062, 2013.

Onami H, Nagai N, Kaji H, Nishizawa M, Sato Y, Osumi N, Nakazawa T, Abe T. Transscleral sustained vasohibin-1 delivery by a novel device suppressed experimentally-induced choroidal neovascularization. PLoS One 8, e58580, 2013.

Yazdani S, Miki Y, Tamaki K, Ono K, Iwabuchi E, Abe K, Suzuki T, Sato Y, Kondo T, Sasano H. Proliferation and maturation of intra-tumoral blood vessels in non-small cell lung cancer. Human Pathol. 44, 1586-1596, 2013.

Kanomata N, Sato Y, Miyaji Y, Nagai A, Moriya T. Vasohibin-1 is a new predictor of disease-free survival in operated renal cell carcinoma patients. J. Clin. Pathol. 66, 613-619, 2013.

Kosaka T, Miyazaki Y, Miyajima A, Mikami S, Hayashi Y, Tanaka N, Nagata H, Kikuchi E, Nakagawa K, Okada Y, Sato Y, Oya M. The prognostic significance of vasohibin-1 expression in patients with prostate cancer. Br J Cancer 108, 2123-2139, 2013.

Ito S, Miyashita H, Suzuki Y, Kobayashi M, Satomi S, Sato Y. Enhanced cancer metastasis in mice deficient in vasohibin-1 gene. PLoS One 16, e73931, 2013.

Koyanagi T, Suzuki Y, Saga Y, Machida S, Takei Y, Fujiwara H, Suzuki M, Sato Y. In vivo delivery of siRNA targeting vasohibin-2 decreases tumor angiogenesis and suppresses tumor growth in ovarian cancer. Cancer Sci. 104, 1705-1710, 2013.

Sato Y. The Vasohibin Family: A Novel Family for Angiogenesis Regulation. J Biochem. 153, 5-11. 2013.

Sato Y. Is Histone Deacetylase-9-MicroRNA-17~92 Cluster a Novel Axis for Angiogenesis Regulation? Arterioscler Thromb Vasc Biol. 33, 445-446, 2013.

2014
Murakami K, Kasajima A, Kawagishi N, Sekiguchi S, Fujishima F, Watanabe M, Sato Y, Ohuchi N, Sasano H. The prognostic significance of vasohibin-1-associated angiogenesis in patients with hepatocellular carcinoma. Human Pathol. 45: 589-597, 2014.

Yazdani S, Kasajima A, Tamaki K, Nakamura Y, Fujishima F, Ohtsuka H, Motoi F, Unno M, Watanabe M, Sato Y, Sasano H. Angiogenesis and vascular maturation in neuroendocrine tumors. Human Pathol. 45: 866-874, 2014.

Kitahara S, Suzuki Y, Morishima M, Yoshii A, Kikuta S, Shimizu K, Morikawa S, Sato Y, Ezaki T. Vasohibin-2 modulates tumor onset in the gastrointestinal tract by normalizing tumor angiogenesis. Mol. Cancer 13: 99, 2014.

Hinamoto N, Maeshima Y, Saito D, Yamasaki H, Tanabe K, Nasu T, Watatani H, Ujike H, Kinomura M, Sugiyama H, Sonoda H, Sato Y, Makino H. Urinary and plasma levels of vasohibin-1 can predict renal functional deterioration in patients with renal disorders. PLoS One 9: e96932, 2014.

Watatani H, Maeshima Y, Hinamoto N, Yamasaki H, Ujike H, Tanabe K, Sugiyama H, Otsuka F, Sato Y, Makino H. Vasohibin-1 deficiency enhances renal fibrosis and inflammation after unilateral ureteral obstruction. Physiol. Rep. 2: e12054, 2014.

Hinamoto N, Maeshima Y, Saito D, Yamasaki H, Tanabe K, Nasu T, Watatani H, Ujike H, Kinomura M, Sugiyama H, Sonoda H, Kanomata N, Sato Y, Makino H. Renal distribution of vasohibin-1 in patients with chronic kidney disease. Acta Med Okayama. 68: 219-241, 2014.

Suenaga K, Kitahara S, Suzuki Y, Kobayashi M, Horie S, Sugawara J, Yaegashi N, Sato Y. Role of the vasohibin family in the regulation of fetoplacental vascularization and syncytiotrophoblast formation. PLoS One 9: e104728, 2014.

Hinamoto N, Maeshima Y, Tanabe K, Nasu T, Saito D, Yamasaki H, Watatani H, Ujike H, Kinomura M, Sugiyama H, Sato Y, Makino H. Exacerbation of diabetic renal alterations in mice lacking vasohibin-1. PLoS One 9: e107934, 2014.

Nakamura T, Suzuki Y, Takahashi Y, Satomi S, Sato Y. Paradoxical augmentation of tumor angiogenesis combined with down-regulation of IP-10 after adenovirus-mediated transfer of vasohibin-1 gene in cancer cells. J. Cancer Sci. Ther. 6: 289-297, 2014.

Sato Y. The Vasohibin Family: The Vasohibin Family: Novel Regulators of Angiogenesis. In “Angiogenesis and Vascularisation” pp 261-267, 2014.

2015
Fukumitsu R, Minami M, Yoshida K, Nagata M, Yasui M, Higuchi S, Fujikawa R, Ikedo T, Yamagata S, Sato Y, Arai H, Yokode M, Miyamoto S. Expression of Vasohibin-1 in Human Carotid Atherosclerotic Plaque. J Atheroscler Thromb. 22: 942-948, 2015.

Kim JC, Kim KT, Park JT, Kim HJ, Sato Y, Kim HS. Expression of vasohibin-2 in pancreatic ductal adenocarcinoma promotes tumor progression and is associated with a poor clinical outcome. Hepatogastroenterology. 62: 251-256, 2015.

Furutani Y, Shiozaki-Sato Y, Hara M, Sato Y, Kojima S. Hepatic fibrosis and angiogenesis after bile duct ligation are endogenously expressed vasohibin-1 independent. Biochem Biophys Res Commun. 463: 384-388, 2015.

Takahashi Y, Saga Y, Koyanagi T, Takei Y, Machida S, Taneichi A, Mizukami H, Sato Y, Matsubara S, Fujiwara H. The angiogenesis regulator vasohibin-1 inhibits ovarian cancer growth and peritoneal dissemination and prolongs host survival. Int J Oncol. 47: 2057-63, 2015.

Sato Y. A novel link between inhibition of angiogenesis and tolerance to vascular stress. J Atheroscler Thromb. 22, 327-334, 2015.

2016
Takahashi Y, Saga Y, Koyanagi T, Takei Y, Machida S, Taneichi A, Mizukami H, Sato Y, Matsubara S, Fujiwara H. Vasohibin-1 expression inhibits advancement of ovarian cancer producing various angiogenic factors. Caner Sci. 2016 [Epub ahead of print].

Horie S, Suzuki Y, Kobayashi M, Kadonosono T, Kondoh S, Kodama T, Sato Y. Distinctive role of vasohibin-1A and its splicing variant vasohibin-1B in tumor angiogenesis. Cancer Gene Ther. 2016 [Epub ahead of print].

Saito M, Suzuki Y, Yano S, Miyazaki T, Sato Y. Proteolytic inactivation of anti-angiogenic vasohibin-1 by cancer cells. J. Biochem. 2016 (in press).

Takeda E, Suzuki Y, Sato Y. Age-associated down-regulation of vasohibin-1 in vascular endothelial cells. Aging Cell 2016 (in press).