Discoery of mechanism for peritoneal metastasis of gastric cancer: targeting cross talk between cancer cell and omentum

• Project/Area Number: 15K15295
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Nagoya City University
• Principal Investigator: Shimura Takaya 名古屋市立大学, 大学院医学研究科, 講師 (90405192)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: 胃癌 / 腹膜転移 / 脂肪 / 大網 / 血管新生 / 微小環境

Outline of Final Research Achievements

Conditioned media (CM) derived from OmAd (OmAd-CM) significantly promoted proliferation and migration of GC cells compared to control media. OmAd-CM also reinforced the ability of GC cells inducing EC recruitment and tube formation. The cytokine array identified that protein-X was abundantly contained in OmAd-CM and "Y" is the most expressed among X family. Silencing "Y" from OmAd (siRNA-OmAd) inhibited OmAd-induced cell growth and migration in both GC cell lines, as well as angiogenesis. This phenomenon was validated with xenograft study and human pathological study.

Academic Significance and Societal Importance of the Research Achievements

胃癌は進行すると高頻度に腹膜転移をきたすが、そのメカニズムは全く不明であることから治療法も限定される。また腹膜転移はCTなどの画像所見にも映らず、診断も困難を極める。
本研究結果により、胃癌が高頻度に腹膜転移をきたす一因を解明できたことにより、今後の新たな治療標的や腹膜転移の診断法の開発につながることが期待される。

Research Products

• [Journal Article] Urinary Cysteine-Rich Protein 61 and Trefoil Factor 3 as Diagnostic Biomarkers for Colorectal Cancer. (2019)
  • Author(s): Shimura T, Iwasaki H, Kitagawa M, Ebi M, Yamada T, Yamada T, Katano T, Nisie H, Okamoto Y, Ozeki K, Mizoshita T, Kataoka H.
  • Journal Title: Transl Oncol. Volume: 12(3) Issue: 3 Pages: 539-544
  • DOI: 10.1016/j.tranon.2018.12.006
  • Peer Reviewed / Open Access
• [Journal Article] Placental growth factor is a predictive biomarker for ramucirumab treatment in advanced gastric cancer. (2019)
  • Author(s): Natsume M, Shimura T, Iwasaki H, Okuda Y, Kitagawa M, Okamoto Y, Hayashi K, Kataoka H
  • Journal Title: Cancer Chemother Pharmacol. Volume: Mar 21. Issue: 6 Pages: 1037-1046
  • DOI: 10.1007/s00280-019-03817-2
  • Peer Reviewed / Open Access
• [Journal Article] Long-term Outcomes of One Stage Surgery Using Transanal Colorectal Tube for Acute Colorectal Obstruction of Stage II/III Distal Colon Cancer. (2019)
  • Author(s): Okuda Y, Yamada T, Hirata Y, Shimura T, Yamaguchi R, Sakamoto E, Sobue S, Nakazawa T, Kataoka H, Joh T.
  • Journal Title: Cancer Res Treat. Volume: Apr;51(2) Issue: 2 Pages: 474-482
  • DOI: 10.4143/crt.2018.059
  • Peer Reviewed / Open Access
• [Journal Article] Colorectal obstruction is a potential prognostic factor for stage II colorectal cancer. (2018)
  • Author(s): Okuda Y, Shimura T, Yamada T, Hirata Y, Yamaguchi R, Sakamoto E, Kataoka H.
  • Journal Title: Int J Clin Oncol. Volume: 23(6) Issue: 6 Pages: 1101-1111
  • DOI: 10.1007/s10147-018-1307-2
  • Peer Reviewed
• [Journal Article] Excellent antitumor effects for gastrointestinal cancers using photodynamic therapy with a novel glucose conjugated chlorin e6 (2018)
  • Author(s): Nishie Hirotada、Kataoka Hiromi、Yano Shigenobu、Yamaguchi Hiroaki、Nomoto Akihiro、Tanaka Mamoru、Kato Akihisa、Shimura Takaya、Mizoshita Tsutomu、Kubota Eiji、Tanida Satoshi、Joh Takashi
  • Journal Title: Biochem Biophys Res Commun. Volume: 496 Issue: 4 Pages: 1204-1209
  • DOI: 10.1016/j.bbrc.2018.01.171
  • Peer Reviewed / Open Access
• [Journal Article] Urinary kallikrein 10 predicts the incurability of gastric cancer. (2017)
  • Author(s): Shimura T, Ebi M, Yamada T, Yamada T, Katano T, Nojiri Y, Iwasaki H, Nomura S, Hayashi N, Mori Y, Kataoka H, Moses MA, Joh T.
  • Journal Title: Oncotarget Volume: Apr 25;8(17) Issue: 17 Pages: 29247-29257
  • DOI: 10.18632/oncotarget.16453
  • Peer Reviewed / Open Access
• [Journal Article] Evidence-based Clinical Management of Acute Malignant Colorectal Obstruction. (2016)
  • Author(s): Shimura T, Joh T
  • Journal Title: J Clin Gastroenterol. Volume: Apr;50(4) Issue: 4 Pages: 273-285
  • DOI: 10.1097/mcg.0000000000000475
  • Peer Reviewed
• [Journal Article] Immunogenic cell death due to a new photodynamic therapy with glycoconjugated chlorin (2016)
  • Author(s): Tanaka M, Kataoka H, Yano S, Sawada T, Akashi H, Inoue M, Suzuki S, Inagaki Y, Hayashi N, Nishie H, Shimura T, Mizoshita T, Mori Y, Kubota E, Tanida S, Takahashi S, Joh T.
  • Journal Title: Oncotarget Volume: 26; 7(30) Issue: 30 Pages: 47242-47251
  • DOI: 10.18632/oncotarget.9725
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Anticancer Effects of a New Aminosugar-conjugated PlatinumComplex Agent Against Cisplatin-resistant Gastric Cancer. (2016)
  • Author(s): Hayashi N, Kataoka H, Yano S, Kikuchi JI, Tanaka M, Nishie H, Kinoshita Y, Hatano M, Nomoto A, Ogawa A, Inoue M, Mizoshita T, Shimura T, Mori Y, Kubota E, Tanida S, Joh T.
  • Journal Title: Anticancer Res. Volume: Nov;36(11) Pages: 6005-6009
  • Peer Reviewed
• [Journal Article] Urinary ADAM12 and MMP-9/NGAL complex detect the presence of gastric cancer. (2015)
  • Author(s): Shimura T, Dagher A, Sachdev M, Ebi M, Yamada T, Yamada T, Joh T, Moses MA.
  • Journal Title: Cancer Prevention Research Volume: 8(3) Issue: 3 Pages: 240-248
  • DOI: 10.1158/1940-6207.capr-14-0229
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Multicenter, prospective trial of white-light imaging alone versus white-light imaging followed by magnifying endoscopy with narrow-band imaging for the real-time imaging and diagnosis of invasion depth in superficial esophageal squamous cell carcinoma. (2015)
  • Author(s): Ebi M, Shimura T, Yamada T, Mizushima T, Itoh K, Tsukamoto H, Tsuchida K, Hirata Y, Murakami K, Kanie H, Nomura S, Iwasaki H, Kitagawa M, Takahashi S, Joh T.
  • Journal Title: Gastrointestinal Endoscopy Volume: 81(6) Issue: 6 Pages: 1355-1361
  • DOI: 10.1016/j.gie.2014.11.015
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Subset Analysis of a Multicenter, Randomized Controlled Trial to Compare Magnifying Chromoendoscopy with Endoscopic Ultrasonography for Stage Diagnosis of Early Stage Colorectal Cancer. (2015)
  • Author(s): Yamada T, Shimura T, Ebi M, Hirata Y, Nishiwaki H, Mizushima T, Asukai K, Togawa S, Takahashi S, Joh T.
  • Journal Title: PLoS One Volume: 10(8) Issue: 8 Pages: e0134942-e0134942
  • DOI: 10.1371/journal.pone.0134942
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Colorectal obstruction is a potential prognostic factor for stage II/III colorectal cancer. (2017)
  • Author(s): Shimura T, Okuda Y, Yamada T, Hirata Y, Yamaguchi R, Sakamoto E, Joh T.
  • Organizer: ESMO Asia 2017
  • Int'l Joint Research
• [Presentation] Urinary Kallikrein-10 predicts incurability of gastric cancer. (2016)
  • Author(s): 志村 貴也
  • Organizer: UEGW 2016
  • Place of Presentation: ウィーン （オーストリア）
  • Year and Date: 2016-10-15
  • Int'l Joint Research
• [Presentation] Urinary ADAM12 and MMP-9/NGAL complex detect the presence of gastric cancer (2015)
  • Author(s): 志村 貴也
  • Organizer: Digestive Disease Week 2015
  • Place of Presentation: ワシントンD.C.(アメリカ）
  • Year and Date: 2015-05-16
  • Int'l Joint Research