Fluorescent virus-guided capturing of epithelial-mesenchymal transition (EMT)-induced circulating tumor cells (CTCs) for genetic analysis

• Project/Area Number: 25670580
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Okayama University
• Principal Investigator: FUJIWARA Toshiyoshi 岡山大学, 医歯(薬)学総合研究科, 教授 (00304303)
• Co-Investigator(Kenkyū-buntansha): KAGAWA Shunsuke 岡山大学, 大学病院, 准教授 (00362971) ; SHIRAKAWA Yasuhiro 岡山大学, 大学院医歯薬学総合研究科, 准教授 (60379774)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 循環癌細胞 / 上皮間葉転換 / テロメラーゼ / アデノウイルス / TGF-beta / GFP / 遺伝子解析 / PCR

Outline of Final Research Achievements

Molecular-based companion diagnostic tests are being used with increasing frequency to predict their clinical response to various drugs. However, invasive procedures are typically required to obtain tissues for this analysis. Here we established a new approach to capture live circulating tumor cells (CTCs) among millions of peripheral blood leukocytes using a GFP-expressing attenuated adenovirus, in which the telomerase promoter regulates viral replication (TelomeScan). Because current CTC detection strategies mainly depend on epithelial cell surface markers, the presence of heterogeneous populations of CTCs with epithelial and/or mesenchymal characteristics may pose obstacles to the detection of CTCs. Our biological capturing system can image both epithelial and mesenchymal tumor cells with telomerase activities as GFP-positive cells. This fluorescent virus-guided viable CTC capturing method provides a non-invasive alternative to tissue biopsy.

Research Products

• [Journal Article] Biological ablation of sentinel lymph node metastasis in submucosally invaded early gastrointestinal cancer. (2015)
  • Author(s): Kikuchi S, Kishimoto H, Tazawa H, Hashimoto Y, Kuroda S, Nishizaki M, Nagasaka T, Shirakawa Y, Kagawa S, Urata Y, Hoffman RM, Fujiwara T.
  • Journal Title: Mol Ther. Volume: 23(3) Issue: 4 Pages: 501-509
  • DOI: 10.1136/gutjnl-2014-306957
  • NAID: 120005537574
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Biological ablation of sentinel lymph node metastasis in submucosally invaded early gastrointestinal cancer. (2015)
  • Author(s): Kikuchi S, et al.
  • Journal Title: Molecular Therapy Volume: 23 Issue: 3 Pages: 501-509
  • DOI: 10.1038/mt.2014.244
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Establishment of a non-invasive semi-quantitative bioluminescent imaging method for monitoring of an orthotopic esophageal cancer mouse model. (2014)
  • Author(s): Kuroda S, et al.
  • Journal Title: PLoS One Volume: 9 Issue: 12 Pages: e114562-e114562
  • DOI: 10.1371/journal.pone.0114562
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Selective methioninase-induced trap of cancer cells in S/G2 phase visualized by FUCCI imaging confers chemosensitivity. (2014)
  • Author(s): Yano S, et al.
  • Journal Title: Oncotarget Volume: 5 Pages: 8729-8736
  • Peer Reviewed
• [Journal Article] Spatial-temporal FUCCI imaging of each cell in a tumor demonstrates locational dependence of cell cycle dynamics and chemoresponsiveness. (2014)
  • Author(s): Yano S, et al.
  • Journal Title: Cell Cycle Volume: 13 Issue: 13 Pages: 2110-2119
  • DOI: 10.4161/cc.29156
  • Peer Reviewed
• [Journal Article] Dual programmed cell death pathways induced by p53 transactivation overcome resistance to oncolytic adenovirus in human osteosarcoma cells. (2013)
  • Author(s): Hasei, J.
  • Journal Title: Molecular Cancer Therapeutics Volume: 12 Issue: 3 Pages: 314-325
  • DOI: 10.1158/1535-7163.mct-12-0869
  • Peer Reviewed
• [Journal Article] A novel synergistic effect of iron depletion on antiangiogenic cancer therapy. (2013)
  • Author(s): Ohara T, Noma K, Urano S, Watanabe S, Nishitani S, Tomono Y, Kimura F, Kagawa S, Shirakawa Y, Fujiwara T
  • Journal Title: International Journal of Cancer Volume: 132 Issue: 11 Pages: 2705-2713
  • DOI: 10.1002/ijc.27943
  • Peer Reviewed
• [Journal Article] Multicenter phase II study of S-1 and docetaxel combination chemotherapy for advanced or recurrent gastric cancer patients with peritoneal dissemination. (2013)
  • Author(s): Shigeyasu, K.
  • Journal Title: Cancer Chemotherapy and Pharmacology Volume: 71 Issue: 4 Pages: 937-943
  • DOI: 10.1007/s00280-013-2086-0
  • Peer Reviewed
• [Journal Article] A genetically engineered oncolytic adenovirus decoys and lethally traps quiescent cancer stem-like cells into S/G2/M-phases. (2013)
  • Author(s): Yano S, Tazawa H, Hashimoto Y, Shirakawa Y, Kuroda S, Nishizaki M, Kishimoto H, Uno F, Nagasaka T, Urata Y, Kagawa S, Hoffman RM, Fujiwara T
  • Journal Title: Clin Cancer Res Volume: 19 Issue: 23 Pages: 6495-6505
  • DOI: 10.1158/1078-0432.ccr-13-0742
  • Peer Reviewed
• [Journal Article] A simple detection system for adenovirus receptor expression using a telomerase-specific replication-competent adenovirus (2012)
  • Author(s): Sasaki, T.
  • Journal Title: Gene Therapy Volume: (Epub ahead of print) Issue: 1 Pages: 112-118
  • DOI: 10.1038/gt.2011.213
  • Peer Reviewed
• [Presentation] 胃癌における蛍光発現ウイルスによる腹腔洗浄液診断：生物学的悪性度指標としての可能性. (2013)
  • Author(s): 香川俊輔
  • Organizer: 第113回日本外科学会定期学術集会（シンポジウム）
  • Place of Presentation: 福岡
• [Presentation] テロメラーゼ活性を指標とする血中遊離癌細胞の高感度検出法の開発と遺伝子解析技術への応用. (2013)
  • Author(s): 重安邦俊
  • Organizer: 第113回日本外科学会定期学術集会（ワークショップ）
  • Place of Presentation: 福岡