健康医療科学分野（越川研究室）

最近の業績と参考文献

論文

Sato S, Nakagawa M, Terashima T, Morinaga S, Miyagi Y, Yoshida E, Yoshimura T, Seiki M, Kaneko S, Ueno M, Yamashita T, Koshikawa N.
EphA2 proteolytic fragment as a sensitive diagnostic biomarker for very early-stage pancreatic ductal carcinoma
Cancer Res. Commun. in press.
Ikeda K, Kaneko R, Tsukamoto E, Funahashi N, Koshikawa N.
Proteolytic cleavage of membrane proteins by membrane type-1 MMP regulates cancer malignant progression.
Cancer Sci. 2023 Feb;114(2):348-356.doi: 10.1111/cas.15638..
Koizumi M, Sato S, Yoshihara M, Nakamura Y, Terao H, Okubo Y, Washimi K,
Yoshioka E, Yokose T, Kishida T, Koshikawa N, Miyagi Y.
Chronological change in EphA2 protein expression Is associated with recurrence of bladder cancer.
Anticancer Res. 2022 Anticancer Res.doi: 10.21873/anticanres.16085..
Karashima T, Umemoto S, Kishida T, Osaka K, Nakagawa M, Yoshida E, Yoshimura T, Sakaguchi M, Nishimoto H, Tai M, Inoue K, Seiki M, Koshikawa N, Shuin T.
Clinical evaluation of urine laminin-γ2 monomer as a potent biomarker for non-muscle invasive bladder cancer.
Cancer Med. 2022 Aug 4. doi: 10.1002/cam4.5087.
Mizuki Yamamoto, Jin Gohda, Ayako Kobayashi, Keiko Tomita, Youko Hirayama, Naohiko Koshikawa, Motoharu Seiki, Kentaro Semba, Tetsu Akiyama, Yasushi Kawaguchi and Jun-ichiro Inoue.
Metalloproteinase-dependent and TMPRSS2-independent cell surface entry pathway of SARS-CoV-2 requires the furin-cleavage site and the S2 domain of spike protein.
mBio. 2022 Jun 16:e0051922. doi: 10.1128/mbio.00519-22.
Hoshino D, Katoh H, Fukumura K, Mayeda A, Miyagi Y, Seiki M and Koshikawa N.
Novel LAMC2 fusion protein has tumor promoting properties in ovarian carcinoma．
Cancer Sci. 2021 Dec;112(12):4957-4967; doi: 10.1111/cas.15149.
Asakura N, Nakamura N, Muroi A, Nojima Y, Yamashita T, Kaneko S, Ikeda K, Koshikawa N,* and Suzuki T.*
Expression of Cancer Stem Cell Markers EpCAM and CD90 Is Correlated with Anti- and Pro-Oncogenic EphA2 Signaling in Hepatocellular Carcinoma. （*責任著者）
Int. J. Mol. Sci. 2021, 22(16), 8652; doi.org/10.3390/ijms22168652.
Yamashita T, Koshikawa N, Shimakami T, Terashima T, Nakagawa M, Nio K, Horii R, Iida N, Kawaguchi K, Arai K, Sakai Y, Yamashita T, Mizukoshi E, Honda M, Kitao A, Kobayashi S, Takahara S, Imai Y, Yoshimura K, Murayama T, Nakamoto Y, Yoshida E, Yoshimura T, Seiki M, and Shuichi Kaneko.
Serum laminin γ2 monomer as a novel diagnostic and predictive biomarker for hepatocellular carcinoma.
Hepatology 2021 Aug;74(2):760-775. doi: 10.1002/hep.31758. Epub 2021 Apr 28.PMID: 33609304
Osumi H, Muroi A, Sakahara M, Kawachi H, Okamoto T, Natsume Y, Yamanaka H, Takano H, Kusama D, Shinozaki E, Ooki A, Yamaguchi K, Ueno M, Takeuchi K, Noda T, Nagayama S, Koshikawa N, Yao R.
Evaluation of the RAS signaling network in response to MEK inhibition using organoids derived from a familial adenomatous polyposis patient.
Sci Rep. 2020 Oct 15;10(1):17455. doi: 10.1038/s41598-020-74530-x.
Yoshida T, Suganuma N, Sato S, Toda S, Nakayama H, Masudo K, Okubo Y, Hayashi H, Yokose T, Koshikawa N, Rino Y, Iwasaki H, Miyagi Y, Masuda M, Hoshino D.
Membrane type 1 matrix metalloproteinase regulates anaplastic thyroid carcinoma cell growth and invasion into the collagen matrix.
Biochem Biophys Res Commun. 2020 Sep 3;529(4):1195-1200. doi: 10.1016/j.bbrc.2020.06.043.
Nagano M, Hoshino D, Toshima J, Seiki M, Koshikawa, N.
NH2-terminal fragment of ZF21 protein suppresses tumor invasion via inhibiting the interaction of ZF21 with FAK:
Cancer Sceince in press.
Sato A, Kakinuma S, Miyoshi M, Kamiya A, Tsunoda T, Kaneko S, Tsuchiya J,Shimizu T, Takeichi E, Nitta S, Kawai-Kitahata F, Murakawa M, Itsui Y, NakagawaM, Azuma S, Koshikawa N, Seiki M, Nakauchi H, Asahina Y, Watanabe M.
Vasoactive Intestinal Peptide Derived From Liver Mesenchymal Cells Mediates Tight Junction Assembly in Mouse Intrahepatic Bile Ducts.
Hepatol Commun. 2019 Dec 24;4(2):235-254. doi: 10.1002/hep4.1459.
Suzuki M, Muroi A, Nojima M, Numata A, Takasaki H, Sakai R, Yokose T, Miyagi Y, Koshikawa N.
Utility of a Reverse Phase Protein Array to Evaluate Multiple Biomarkers in Diffuse Large B-Cell Lymphoma.
Proteomics Clin Appl. 2020 Jan;14(1):e1900091. doi: 10.1002/prca.201900091.
Yasuda H, Nakagawa M, Kiyokawa H, Yoshida E, Yoshimura T, Koshikawa N, Itoh F, Seiki M.
Unique Biological Activity and Potential Role of Monomeric Laminin-γ2 as a Novel Biomarker for Hepatocellular Carcinoma: A Review.
Int J Mol Sci. 2019 Jan 8;20(1):226. doi: 10.3390/ijms20010226.
Takahashi Y, Hamasaki M, Aoki M, Koga K, Koshikawa N, Miyamoto S, Nabeshima K.
Activated EphA2 Processing by MT1-MMP Is Involved in Malignant Transformation of Ovarian Tumours In Vivo.
Anticancer Res. 2018 Jul;38(7):4257-4266. doi: 10.21873/anticanres.
Kikuchi K, Kozuka-Hata H, Oyama M, Seiki M, Koshikawa N.
Identification of Proteolytic Cleavage Sites of EphA2 by Membrane Type 1 Matrix Metalloproteinase on the Surface of Cancer Cells.
Methods Mol Biol. 2018;1731:29-37. doi:10.1007/978-1-4939-7595-2_3.
Koshikawa N, Minegishi T, Kiyokawa H, Seiki M.
Specific detection of soluble EphA2 fragments in blood as a new biomarker for pancreatic cancer.
Cell Death Dis. 2017 Oct 26;8(10):e3134. doi: 10.1038/cddis.2017.545.
Nakagawa M, Karashima T, Kamada M, Yoshida E, Yoshimura T, Nojima M, Inoue K, Shuin T, Seiki M, Koshikawa N.
Development of a fully automated chemiluminescence immunoassay for urine monomeric laminin-γ2 as a promising diagnostic tool of non-muscle invasive bladder cancer.
Biomarker Res. 2017 Oct 13;5:29. doi: 10.1186/s40364-017-0109-4.
Suzuki T, Minerva D, Nishiyama K, Koshikawa N,
Chaplain MAJ. Study on the tumor-induced angiogenesis using mathematical models.
Cancer Sci. 2018 Jan;109(1):15-23. doi: 10.1111/cas.13395.
Kiyokawa H, Yasuda H, Oikawa R, Okuse C, Matsumoto N, Ikeda H, Watanabe T, Yamamoto H, Itoh F, Otsubo T, Yoshimura T, Yoshida E, Nakagawa M, Koshikawa N, Seiki M.
Serum monomeric laminin-γ2 as a novel biomarker for hepatocellular carcinoma.
Cancer Sci. 2017 Jul;108(7):1432-1439. doi: 10.1111/cas.13261.
Tatsukawa R, Koga K, Aoki M, Koshikawa N, Imafuku S, Nakayama J, Nabeshima K.
Immunohistochemical demonstration of EphA2 processing by MT1-MMP in invasive cutaneous squamous cell carcinoma.
Virchows Arch. 2016 Jul;469(1):25-34. doi: 10.1007/s00428-016-1934-9.
Otani S, Kakinuma S, Kamiya A, Goto F, Kaneko S, Miyoshi M, Tsunoda T, Asano Y, Kawai-Kitahata F, Nitta S, Nakata T, Okamoto R, Itsui Y, Nakagawa M, Azuma S, Asahina Y, Yamaguchi T, Koshikawa N, Seiki M, Nakauchi H, Watanabe M.
Matrix metalloproteinase-14 mediates formation of bile ducts and hepatic maturation of fetal hepatic progenitor cells.
Biochem Biophys Res Commun. 2016 Jan 22;469(4):1062-8. doi: 10.1016/j.bbrc.2015.12.105.
Kamada M, Koshikawa N, Minegishi T, Kawada C, Karashima T, Shuin T, Seiki M.
Urinary laminin-γ2 is a novel biomarker of non-muscle invasive urothelial carcinoma.
Cancer Sci. 2015 Dec;106(12):1730-7. doi: 10.1111/cas.12832.
Koshikawa N, Hoshino D, Taniguchi H, Minegishi T, Tomari T, Nam SO, Aoki M, Sueta T, Nakagawa T, Miyamoto S, Nabeshima K, Weaver AM, Seiki M.
Proteolysis of EphA2 Converts It from a Tumor Suppressor to an Oncoprotein.
Cancer Res. 2015 Aug 15;75(16):3327-39. doi: 10.1158/0008-5472.CAN-14-2798.
Kikuchi K, Noguchi A, Kasajima R, Miyagi Y, Hoshino D, Koshikawa N, Kubota A, Yokose T, Takano Y.
Association of SIRT1 and tumor suppressor gene TAp63 expression in head and neck squamous cell carcinoma.
Tumour Biol. 2015 Sep;36(10):7865-72. doi: 10.1007/s13277-015-3515-y.
Ito-Kureha T, Koshikawa N, Yamamoto M, Semba K, Yamaguchi N, Yamamoto T, Seiki M, Inoue J.
Tropomodulin 1 expression driven by NF-κB enhances breast cancer growth.
Cancer Res. 2015 Jan 1;75(1):62-72. doi: 10.1158/0008-5472.CAN-13-3455.
Koshikawa N, Mizushima H, Minegishi T, Eguchi F, Yotsumoto F, Nabeshima K, Miyamoto S, Mekada E, Seiki M.
Proteolytic activation of heparin-binding EGF-like growth factor by membrane-type matrix metalloproteinase-1 in ovarian carcinoma cells.
Cancer Sci. 2011 Jan;102(1):111-6. doi:10.1111/j.1349-7006.
Koshikawa N, Mizushima H, Minegishi T, Iwamoto R, Mekada E, Seiki M.
Membrane type 1-matrix metalloproteinase cleaves off the NH2-terminal portion of heparin-binding epidermal growth factor and converts it into a heparin-independent growth factor.
Cancer Res. 2010 Jul 15;70(14):6093-103. doi:10.1158/0008-5472.CAN-10-0346.
Niiya D, Egawa N, Sakamoto T, Kikkawa Y, Shinkawa T, Isobe T, Koshikawa N, Seiki M.
Identification and characterization of Lutheran blood group glycoprotein as a new substrate of membrane-type 1 matrix metalloproteinase 1 (MT1-MMP): a systemic whole cell analysis of MT1-MMP-associating proteins in A431 cells.
J Biol Chem. 2009 Oct 2;284(40):27360-9. doi:10.1074/jbc.M109.029124.
Tomari T, Koshikawa N, Uematsu T, Shinkawa T, Hoshino D, Egawa N, Isobe T,Seiki M.
High throughput analysis of proteins associating with a proinvasive MT1-MMP in human malignant melanoma A375 cells.
Cancer Sci. 2009 Jul;100(7):1284-90. doi: 10.1111/j.1349-7006.2009.01173.x.
Koshikawa N, Minegishi T, Nabeshima K, Seiki M.
Development of a new tracking tool for the human monomeric laminin-gamma 2 chain in vitro and in vivo.
Cancer Res. 2008 Jan 15;68(2):530-6. doi: 10.1158/0008-5472.CAN-07-5269.
Koshikawa N, Giannelli G, Cirulli V, Miyazaki K, Quaranta V.
Role of cell surface metalloprotease MT1-MMP in epithelial cell migration over laminin-5.
J Cell Biol. 2000 Feb 7;148(3):615-24. doi: 10.1083/jcb.148.3.615.
Koshikawa N, Moriyama K, Takamura H, Mizushima H, Nagashima Y, Yanoma S, Miyazaki K.
Overexpression of laminin gamma2 chain monomer in invading gastric carcinoma cells.
Cancer Res. 1999 Nov 1;59(21):5596-601. PMID: 10554040.

日本語専門書

朝倉暢彦、室井　敦、越川直彦、鈴木　貴、肝細胞がんのシグナル伝達と生物統計による層別化Precision medicine, 13、1224-1230、2020.
室井　敦、星野大輔、清木元治、越川直彦、MT1-MMPのプロテアーゼ活性を通じたがん悪性化進展制御（膜タンパク質工学ハンドブック）、2020.
星野大輔、室井　敦、清木元治、越川直彦、がんの悪性化：浸潤と転移、細胞運動と浸潤、がん生物学　イラストレイテッド、P242-261（羊土社）、2019.
越川直彦、細胞外基質を指標とした膀胱がんの新しい診断法の開発、日薬理誌、146、248-251, 2015.
越川直彦、清木元治、膜型マトリックスメタロプロテアーゼの新しい側面と腫瘍マーカー，カレントテラピー、29、45-50, 2011.
越川直彦:改訂版4版蛋白質の実験ノート上巻、無敵のバイオテクニカルシリーズ（羊土社）、125-133, 2011.
越川直彦：がん細胞膜上の微小環境-悪性化制御因子としての膜型マトリックスメタロプロテアーゼ１-、Medical Bio, 52, 4-29, 2011.
越川直彦、清木元治：血管新生とマトリックスメタロプロテアーゼ、実験医学（増刊）、20, 1153-1160, 2002.
越川直彦、清木元治：マトリックスメタロプロテアーゼと癌転移、Molecular Med. 39, 32-38, 2002.
越川直彦、宮田智、宮崎香：続がんの浸潤・転移研究マニュアル、-実験の手技と指針-（金芳堂）168-172 1997.

知財取得、申請

特許成立（8件）

1. Methods Of Diagnosing Hepatocellular Carcinoma And Pancreatic Cancer　 US11340229B2
2. 肝細胞癌および膵臓癌を診断するためのラミニンγ2の使用　特許第6829445 (2021.1.26)
3. EphA2 N末端フラグメント抗体　特許第6729917(2020.7.6)
4. Use of laminin gamma2 for diagnosing hepatocellular carcinoma and pancreatic cancer　 HK 19101868.6 (2019.2.1)
5. がんの予後判定および診断方法　特許第6328103 (2018.4.27)
6. がんの検査方法及び検査用キット　特許第6069806 (2017.1.13)
7. がんの検査方法及び検査用キット　特許第5875054 (2016.1.29)
8. 泌尿器科がんの検査方法及び検査用キット　特許第5754844 (2015.6.5）

特願中（2件）

1. 細胆管増生を伴う肝細胞を検出するためのバイオマーカー特願2021-121616
2. LAMC2-NR6A1スプライシングバリアント及びその翻訳産物特願2020-029791