Therapeutic implication for cancer-associated fibroblasts (CAF) in cholangiocarcinoma

• Project/Area Number: 15K19900
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Kumamoto University
• Principal Investigator: IMAI Katsunori 熊本大学, 医学部附属病院, 助教 (60555746)
• Research Collaborator: OKABE Hirohisa 熊本大学, 医学部附属病院, 非常勤診療医師 (40573621)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 癌関連線維芽細胞（CAF） / 胃癌 / CXCL12 / CXCR4 / 胃接合部癌 / 線維芽細胞 / CAF

Outline of Final Research Achievements

Cancer associated fibroblasts (CAFs) were hardly isolated from human cholangiocarcinoma tissue samples because tissue was stiff and elastic. Instead, CAFs were isolated from human gastric cancer tissues. Activation of CAFs was confirmed by expression of SMA by immunocytochemistry. Three out of six human CAFs overexpressed CXCL12. Co-culture of CXCL12-expressing human CAF and gastric cancer cell line, OACM5.1C expressing CXCR4 induced invasive capacity of cancer cell. On the other hand, this interaction was prohibited by CXCR4 antagonist.

Research Products

• [Journal Article] C5a receptor (CD88) promotes motility and invasiveness of gastric cancer by activating RhoA. (2016)
  • Author(s): Kaida T, Nitta H, Kitano Y, Yamamura K, Arima K, Izumi D, Higashi T, Kurashige J, Imai K, Hayashi H, Iwatsuki M, Ishimoto T, Hashimoto D, Yamashita Y, Chikamoto A, Imanura T, Ishiko T, Beppu T, Baba H.
  • Journal Title: Oncotarget. Volume: 20(7) Issue: 51 Pages: 84798-84809
  • DOI: 10.18632/oncotarget.12656
  • Peer Reviewed
• [Journal Article] Early Recurrence After Hepatectomy for Colorectal Liver Metastases: What Optimal Definition and What Predictive Factors? (2016)
  • Author(s): Imai K, Allard MA, Benitez CC, Vibert E, Sa Cunha A, Cherqui D, Castaing D, Bismuth H, Baba H, Adam R.
  • Journal Title: Oncologist Volume: 21(7) Issue: 7 Pages: 887-94
  • DOI: 10.1634/theoncologist.2015-0468
  • Peer Reviewed
• [Journal Article] Nomogram for prediction of prognosis in patients with initially unresectable colorectal liver metastases. (2016)
  • Author(s): Imai K, Allard MA, Castro Benitez C, Vibert E, Sa Cunha A, Cherqui D, Castaing D, Bismuth H, Baba H, Adam R.
  • Journal Title: Br J Surg Volume: 103(5) Issue: 5 Pages: 590-9
  • DOI: 10.1002/bjs.10073
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Failure to Achieve a 2-Stage Hepatectomy for Colorectal Liver Metastases: How to Prevent It? (2015)
  • Author(s): Imai K, Benitez CC, Allard MA, Vibert E, Cunha AS, Cherqui D, Castaing D, Bismuth H, Baba H, Adam R.
  • Journal Title: Ann Surg. Volume: 262(5) Issue: 5 Pages: 772-8
  • DOI: 10.1097/sla.0000000000001449
  • Peer Reviewed / Int'l Joint Research