Development of new diagnosis and treatment procedures based on chemokine network for esophageal cancer

• Project/Area Number: 24591960
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Keio University
• Principal Investigator: TAKEUCHI Hiroya 慶應義塾大学, 医学部, 准教授 (20265838)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 食道扁平上皮癌 / ケモカイン / CXCL12 / CXCR4 / CXCL8 / CXCR2 / ケモカインレセプター / 食道がん / 再発 / 転移 / 食道癌 / 悪性度

Outline of Final Research Achievements

In this study, we demonstrated that a positive CXCL12 expression correlates significantly with a lower recurrence-free survival rate in our esophageal squamous cell carcinoma (ESCC) patient population. These results suggest that CXCL12 expression in ESCC promotes the proliferation of the tumour and has a direct impact on the recurrence rate independently of invasion or metastasis. Furthermore, the fact that both CXCL12 overexpression and CXCL12 exposure similarly promote proliferation denotes that ESCC cells expressing　CXCL12 secrete this factor and cell proliferation is stimulated by the binding of CXCL12 to CXCR4 on the cell membrane, via autocrine growth.
Increased expression of both CXCL-8 and CXCR-2 correlated with tumor progression, metastasis, higher preoperative levels of proinflammatory cytokines, CRP, activation of exogenous coagulation factors, and poor prognosis in ESCC patients.

Research Products

• [Journal Article] Clinical significance of CXCL-8/CXCR-2 network in esophageal squamous cell carcinoma (2013)
  • Author(s): Ogura M, Takeuchi H, Kawakubo H, Nishi T, Fukuda K, Nakamura R, Takahashi T, Wada N, Saikawa Y, Omori T, Miyasho T, Yamada S, and Kitagawa Y
  • Journal Title: Surgery Volume: 154 Issue: 3 Pages: 512-520
  • DOI: 10.1016/j.surg.2013.06.013
  • Peer Reviewed
• [Presentation] Chemokine and chemokine receptor network in esophageal squamous cell carcinoma (2014)
  • Author(s): Takeuchi H, Uchi Y, Ogura M, Nishi T, Irino T, Matsuda S, Inoue M, Fukuda K, Nakamura R, Takahashi T, Wada N, Kawakubo H, Saikawa Y, Omori T, Kitagawa Y
  • Organizer: 第25回日本消化器癌発生学会総会
  • Place of Presentation: 福岡県福岡市，ホテル日航福岡
  • Year and Date: 2014-11-14
• [Presentation] 食道扁平上皮癌におけるChemokine-Chemokine Receptor発現と予後との関連性に関する検討 (2014)
  • Author(s): 井上正純，竹内裕也，中村理恵子，高橋常浩，和田則仁，川久保博文，才川義朗，大森泰，北川雄光
  • Organizer: 第69回日本消化器外科学会総会
  • Place of Presentation: 福島県郡山市，郡山総合体育館
  • Year and Date: 2014-07-18
• [Presentation] 食道扁平上皮癌におけるChemokine receptor発現と臨床病理学的特徴との関連 (2014)
  • Author(s): 井上正純，竹内裕也，中村理恵子，高橋常浩，和田則仁，川久保博文，才川義朗，大森泰，北川雄光
  • Organizer: 第68回日本食道学会学術集会
  • Place of Presentation: 東京都文京区，東京ドームホテル
  • Year and Date: 2014-07-03
• [Presentation] CXCL12/CXCR4システムが食道扁平上皮癌の増殖・予後に与える影響についての検討
  • Author(s): 内雄介，竹内裕也，松田祐子，川久保博文，中村理恵子，高橋常浩，和田則仁，才川義朗，大森泰，北川雄光
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 北海道，札幌市教育文化会館
• [Presentation] 食道癌におけるCXCL8・CXCR2発現と予後に与える影響
  • Author(s): 小倉正治，竹内裕也，西知彦，川久保博文，中村理恵子，高橋常浩，和田則仁，才川義朗，大森泰，北川雄光
  • Organizer: 第65回日本胸部外科学会定期学術集会
  • Place of Presentation: 福岡県，福岡国際会議場
• [Presentation] 食道癌におけるCXCL8発現と臨床病理学的側面の検討
  • Author(s): 小倉正治，竹内裕也，川久保博文，中村理恵子，高橋常浩，和田則仁，才川義朗，大森泰，北川雄光
  • Organizer: 第50回日本癌治療学会学術集会
  • Place of Presentation: 神奈川県，パシフィコ横浜
• [Presentation] CXCL12-CXCR4 systemと食道扁平上皮癌の増殖・予後との関連についての検討
  • Author(s): 内雄介，竹内裕也，松田祐子，中村理恵子，高橋常浩，川久保博文，和田則仁，才川義朗，大森泰，北川雄光
  • Organizer: 第50回日本癌治療学会学術集会
  • Place of Presentation: 神奈川県，パシフィコ横浜