Chemokine signaling involved in colon cancer progression

• Project/Area Number: 24591975
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyoto University
• Principal Investigator: KAWADA Kenji 京都大学, 医学(系)研究科(研究院), 講師 (90322651)
• 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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 大腸癌 / ケモカイン / 転移 / 浸潤

Outline of Final Research Achievements

Chemokines and their receptors play key roles in leukocyte trafficking and are also implicated in cancer metastasis. By constructing SW620 cell lines with reduced expression of CXCR3 and/or CXCR4 using microRNA, we investigated in vivo metastatic activities in a mouse rectal transplantation model. CXCR3-, CXCR4-, and CXCR3/CXCR4 double-knockdowns significantly reduced metastasis to lymph nodes, liver and lungs, compared with the control. Importantly, its suppressive effect was significantly stronger in CXCR3/CXCR4 double-knockdowns. Clinical specimens of liver metastasis showed a strong inverse correlation between levels of CCL15 and Smad4. Patients with CCL15-expressing metastases showed significantly shorter times of disease-free survival than those with CCL15-negative metastases.

Research Products

• [Journal Article] Loss of SMAD4 from colorectal cancer cells promotes CCL15 expression to recruit CCR1+ myeloid cells and facilitate liver metastasis. (2013)
  • Author(s): Itatani Y, Kawada K, Fujishita T, Kakizaki F, Hirai H, Matsumoto T, Iwamoto M, Inamoto S, Hatano E, Hasegawa S, Maekawa T, Uemoto S, Sakai Y, Taketo MM
  • Journal Title: Gastroenterol Volume: 145(5) Issue: 5 Pages: 1064-1075
  • DOI: 10.1053/j.gastro.2013.07.033
  • NAID: 120005348333
  • Peer Reviewed
• [Journal Article] The role of CXCR3 and CXCR4 in colorectal cancer metastasis. (2012)
  • Author(s): Yuki Nakanishi, et. al.
  • Journal Title: International Journal of Cancer Volume: 132 Issue: 2 Pages: 276-287
  • DOI: 10.1002/ijc.27670
  • Peer Reviewed
• [Presentation] Loss of Smad4 in Colorectal Cancer Promotes CCL15 Expression to Recruit CCR1+ Myeloid Cells and Facilitate Liver Metastasis (2013)
  • Author(s): 板谷喜朗、河田健二、他
  • Organizer: American College of Surgeons
  • Place of Presentation: Washington. DC, USA
• [Remarks] 京都大学医学研究科 消化管外科ホームページ
  • URL: http://gisurg.kuhp.kyoto-u.ac.jp/info