Mechanisms of liver metastasis via alteration of miRNA expression in gastrointinal malignancies

• Project/Area Number: 15K10132
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Kikuchi Hirotoshi 浜松医科大学, 医学部附属病院, 講師 (70397389)
• Co-Investigator(Kenkyū-buntansha): 今野 弘之 浜松医科大学, 医学部, 学長 (00138033)
• Research Collaborator: Murakami Tomohiro 浜松医科大学, 大学院生 ; Ishimatsu Hisato 浜松医科大学, 大学院生 ; Baba Satoshi 浜松医科大学, 医学部附属病院, 病院教授 ; Kitagawa Masatoshi 浜松医科大学, 医学部, 教授 ; Kitagawa Kyoko 浜松医科大学, 医学部, 助教
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: マイクロRNA / 肝転移 / 腫瘍間質 / 微小環境 / tenascin C / 大腸癌 / 腫瘍周囲間質 / 消化管間質腫瘍 / 予後予測マーカー / 癌 / マイクロアレイ / 転移

Outline of Final Research Achievements

To identify mechanisms of liver metastasis, microRNA expression was analyzed in colorectal cancer (CRC) stroma and gastrointestinal stromal tumors (GISTs). In CRC,
suppression of miR-198 in tumor stroma appears to form a metastasis-permissive environment that can elevate tenascin C to promote liver metastasis. Tenascin C expression in CRC stroma was identified as a novel molecular marker of CRC to predict postoperative liver metastasis. In GIST, overexpression of miR-122 and concomitant suppression of CAT1, and suppression of miR-133b and concomitant overexpression of fascin-1 protein appear to play important roles in the development of liver metastasis.

Research Products

• [Journal Article] Tenascin C in colorectal cancer stroma is a predictive marker for liver metastasis and is a potent target of miR-198 as identified by microRNA analysis. (2017)
  • Author(s): Murakami, T., Kikuchi, H., Ishimatsu, H., Iino, I., Hirotsu, A., Matsumoto, T., Ozaki, Y., Kawabata, T., Hiramatsu, Y., Ohta, M., Kamiya, K., Fukushima, M., Baba, S., Kitagawa, K., Kitagawa, M. and Konno H
  • Journal Title: Br J Cancer. Volume: 117(9) Issue: 9 Pages: 1360-1370
  • DOI: 10.1038/bjc.2017.291
  • Peer Reviewed / Open Access
• [Presentation] Tenascin C in colorectal cancer stroma is a predictive marker for liver metastasis and is a potent target of miR-198 as identified by microRNA analysis (2018)
  • Author(s): Tomohiro Murakami, Hirotoshi Kikuchi, Hisahito Ishimatsu, Sanshiro Kawata, Tomohiro Matsumoto, Yusuke Ozaki, Yoshihiro Hiramatsu, Kinji Kamiya, Megumi Baba, Satoshi Baba, Masatoshi Kitagawa, Takanori Sakaguchi, Hiroyuki Konno, Hiroya Takeuchi
  • Organizer: American Association for Cancer Research Annual Meeting 2018
  • Int'l Joint Research
• [Presentation] 大腸癌間質で低下するmiR-198は標的遺伝子tenascin Cの発現を亢進し肝転移を促進している (2018)
  • Author(s): 村上智洋、菊池寛利、曽根田亘、川田三四郎、廣津周、松本知拓、尾﨑裕介、川端俊貴、平松良浩、馬場恵、神谷欣志、森田剛文、坂口孝宣、今野弘之、竹内裕也
  • Organizer: 第118回日本外科学会定期学術集会
• [Presentation] MicroRNA expression analysis in the tumor stroma predicts Tenascin C to promote colorectal liver metastasis. (2017)
  • Author(s): Tomohiro Murakami, Hisahito Ishimatsu, Hirotoshi Kikuchi Amane Hirotsu, Tomohiro Matsumoto, Yusuke Ozaki, Toshiki Kawabata, Yoshihiro Hiramatsu, Kinji Kamiya, Megumi Baba, Takanori Sakaguchi, Hiroyuki Konno
  • Organizer: American Association for Cancer Research Annual Meeting 2017
  • Int'l Joint Research
• [Presentation] 大腸癌周囲の間質で変化するmiRNAの標的遺伝子Tenascin Cは肝転移を促進している (2017)
  • Author(s): 村上智洋、石松久人、菊池寛利、川田三四郎、廣津周、松本知拓、尾崎裕介、川端俊貴、平松良浩、馬場恵、太田学、神谷欣志、坂口孝宣、今野弘之
  • Organizer: 第117回日本外科学会定期学術集会
• [Presentation] 大腸癌周囲の間質におけるmiRNA発現変化とTenascin C発現亢進は肝転移形成に関与する (2017)
  • Author(s): 村上智洋、菊池寛利、廣津周、松本知拓、尾﨑裕介、川端俊貴、平松良浩、神谷欣志、坂口孝宣、今野弘之
  • Organizer: 第72回日本消化器外科学会総会
• [Presentation] 大腸癌周囲間質のマイクロRNAアレイ解析によって同定されたTenascin Cは肝転移の予測因子である (2017)
  • Author(s): 村上智洋、菊池寛利、川田三四郎、廣津周、松本知拓、尾﨑裕介、川端俊貴、平松良浩、馬場恵、神谷欣志、坂口孝宣、今野弘之、竹内裕也
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] 大腸癌周囲の間質で変化するmiRNAの標的遺伝子Tenascin Cは肝転移を促進している (2017)
  • Author(s): 村上智洋、菊池寛利、川田三四郎、廣津周、松本知拓、尾﨑裕介、川端俊貴、平松良浩、神谷欣志、坂口孝宣、今野弘之、竹内裕也
  • Organizer: JDDW 2017
• [Presentation] Alteration of miRNAs and concomitant overexpression of tenascin C in colorectal cancer stroma promote liver metastasis (2017)
  • Author(s): 菊池寛利、村上智洋、川田三四郎、廣津周、松本知拓、尾﨑裕介、川端俊貴、平松良浩、神谷欣志、坂口孝宣、今野弘之、竹内裕也
  • Organizer: 第28回日本消化器癌発生学会総会
• [Presentation] 消化器悪性腫瘍の肝転移におけるマイクロRNAの関与 (2016)
  • Author(s): 菊池寛利、村上智洋、松本知拓、尾崎裕介、川端俊貴、平松良浩、神谷欣志、太田学、坂口孝宣、今野弘之
  • Organizer: JDDW 2016
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2016-11-03
• [Presentation] 胃GISTの肝転移におけるマイクロRNA発現変化の解析 (2016)
  • Author(s): 菊池寛利、廣津周、村上智洋、松本知拓、尾崎祐介、川端俊貴、平松良浩、神谷欣志、太田学、坂口孝宣、今野弘之
  • Organizer: 第27回日本消化器癌発生学会総会
  • Place of Presentation: 鹿児島県鹿児島市
  • Year and Date: 2016-09-15
• [Presentation] 消化管間質腫瘍の肝転移におけるmicroRNA発現変化の解析 (2016)
  • Author(s): 菊池寛利、村上智洋、松本知拓、尾崎祐介、川端俊貴、平松良浩、神谷欣志、太田学、坂口孝宣、今野弘之
  • Organizer: 第25回日本がん転移学会学術集会
  • Place of Presentation: 鳥取県米子市
  • Year and Date: 2016-07-21
• [Presentation] 消化管間質腫瘍の悪性化機序の解明と新規治療標的の探索 (2016)
  • Author(s): 菊池寛利、村上智洋、松本知拓、尾崎裕介、川端俊貴、平松良浩、太田学、神谷欣志、坂口孝宣、今野弘之
  • Organizer: 第71回日本消化器外科学会総会
  • Place of Presentation: 徳島県徳島市
  • Year and Date: 2016-07-14
• [Presentation] Microarray Analysis of Gastrointestinal Stromal Tumor-Originated Spheroids (2016)
  • Author(s): Hirotoshi Kikuchi, Shinichiro Miyazaki, Tomohiro Murakami, Tomohiro Matsumoto, Yusuke Ozaki, Yoshihiro Hiramatsu, Kinji Kamiya, Manabu Ohta, Takanori Sakaguchi, Hiroyuki Konno.
  • Organizer: American Association for Cancer Research Annual Meeting 2016
  • Place of Presentation: New Orleans, LA, USA
  • Year and Date: 2016-04-16
  • Int'l Joint Research
• [Presentation] Differential miRNA expressions between gastric and metastatic liver gastrointestinal stromal tumors (2016)
  • Author(s): Hirotoshi Kikuchi, Ichirota Iino, Shinichiro Miyazaki, Yusuke Ozaki, Yoshihiro Hiramatsu&, Manabu Ohta, Kinji Kamiya, Takanori Sakaguchi, Hiroyuki Konno
  • Organizer: 69th Society of Surgeical Oncology Annual Cancer Symposium
  • Place of Presentation: Boston, MA, USA
  • Year and Date: 2016-03-03
• [Presentation] 消化管間質腫瘍における肝転移再発の予測マーカー・治療標的の探索 (2015)
  • Author(s): 菊池寛利,宮崎真一郎,飯野一郎太,川端俊貴,平松良浩,神谷欣志,太田学,坂口孝宣,今野弘之
  • Organizer: JDDW 2015
  • Place of Presentation: 東京都品川区
  • Year and Date: 2015-10-09