Search of novel biomarkers as prognostic factors focused on the stromal cells in patients with colorectal cancer

• Project/Area Number: 24591978
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Sapporo Medical University
• Principal Investigator: FURUHATA TOMOHISA 札幌医科大学, 保健医療学部, 教授 (80359992)
• Co-Investigator(Kenkyū-buntansha): OKITA Kenji 札幌医科大学, 医学部, 助教 (70517911)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 大腸癌 / 間質細胞 / MMP-2 / EMMPRIN / 線維芽細胞 / FGFR / FGF / EMT

Outline of Final Research Achievements

It has been thought that cancer associated fibroblasts have important roles on invasive behavior of colorectal cancer. MMP-2 expression in fibroblasts and invasive potential in cancer cells are induced in co-culture with fibroblasts and colon cancer cell lines. EMMPRIN produced in cancer cells may induce MMP-2 expression in fibroblasts. Immuno-histochemical staining demonstrates EMMPRIN and MMP-2 expression in half of cases in Stage 2 and 3 colorectal cancer patients. Correlation between EMMPRIN and MMP-2 expression is observed and statistically significant (p=0.025). This results imply that MMP-2 expression in fibroblasts is induced by EMMPRIN originated from cancer cells. We can not find out significant prognostic factors in this series. Both expression of MMP-2 and EMMPRIN may have some trends on survival of patients with Stage 2 and 3 colorectal cancer.

Research Products

• [Journal Article] Oncological benefit of primary tumor resection with high tie lymph node dissection in unresectable colorectal cancer with synchronous peritoneal metastasis: a propensity score analysis of data from a multi-institute database (2015)
  • Author(s): Furuhata T, Okita K, Nishidate T, Hirata K, Ohnishi H, Kobayashi H, Kotake K, Sugihara K
  • Journal Title: Int J Clin Oncol Volume: Epub ahead of print Issue: 5 Pages: 922-927
  • DOI: 10.1007/s10147-015-0815-6
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Clinical feasibility of laparoscopic lateral pelvic lymph node dissection following total mesorectal excision for advanced rectal cancer. (2015)
  • Author(s): Furuhata T, Okita K, Nishidate T, Ito T, Yamaguchi H, Ueki T, Akizuki E, Meguro M, Ogawa T, Kukita K, Kimura Y, Mizuguchi T, Hirata K.
  • Journal Title: Surg Today Volume: 45 Issue: 3 Pages: 310-314
  • DOI: 10.1007/s00595-014-0906-4
  • Peer Reviewed / Open Access
• [Journal Article] Cancer-associated oxidase ERO1-α regulates the expression of MHC class I molecule via oxidative folding. (2015)
  • Author(s): Kazuharu Kukita, Yasuaki Tamura, Tsutomu Tanaka, Toshimitsu Kajiwara, Goro Kutomi, Keita Saito, Koichi Okuya, Akari Takaya, Takayuki Kanaseki, Tomohide Tsukahara, Yoshihiko Hirohashi, Toshihiko Torigoe, Tomohisa Furuhata, Koichi Hirata, Noriyuki Sato
  • Journal Title: J Immunology Volume: 197 Issue: 10 Pages: 0-0
  • DOI: 10.4049/jimmunol.1303228
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] ヒト原発大腸癌組織からの癌幹細胞の分離とその機能的解析 (2014)
  • Author(s): 小川宰司、廣橋良彦、古畑智久、鳥越俊彦、平田公一、佐藤昇志
  • Organizer: 第73回日本癌学会総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] SVN-2B ペプチドがんワクチン第I 相臨床試験“SUCCESS”から得た最新の知見 (2014)
  • Author(s): 島宏彰、水口徹、里見蕗乃、九冨五郎、信岡隆幸、木村康利、古畑智久、廣橋良彦、鳥越俊彦、佐藤昇志、平田公一
  • Organizer: 第73回日本癌学会総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 腫瘍浸潤T 細胞は大腸癌の予後マーカーとなる (2014)
  • Author(s): 藤田知信、徐明利、ポピバノバボリヤナ、岡本正人、桜井敏晴、鳥越俊彦、古畑智久、杉浦史哲、奥野清隆、硲彰一、岡正朗、河上裕
  • Organizer: 第73回日本癌学会総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] MMP-2 expression in stromal tissues is a consistent prognostic factor in Stage2 colon and rectal cancer (2013)
  • Author(s): Tomohisa Furuhata, Kenji Okita, Toshihiko Nishidate, Yoshiko, Tayama, Makoto Tayama, Tomomi Ueki, Tatsuya Ito, Kazuharu Kukita,Hitoshi Zembutsu, Yasutoshi Kimura, Koichi Hirata
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜市
• [Presentation] Expression of CD147(EMMPRIN) and MMP-2 in human colorectal cancer (2013)
  • Author(s): Tomomi Ueki, Toshihiko Nishidate, Kenji Okita, Kazuharu Kukita, Tadashi Ogawa, Tomohisa Furuhata, Kouichi Hirata
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜市
• [Presentation] hERO-1La acts as a risk factor of recurrence via regulation of tumor growth factors under hypoxia in colorectal cancer (2012)
  • Author(s): Kukita K, Tamura Y, Kutomi G, Okuya K, Saito K, Furuhata T, Torigoe T, Hirata K, Sato N
  • Organizer: 第71回日本癌学会総会
  • Place of Presentation: 札幌