Metastasis initiating cell of lung cancer brain metastases

• Project/Area Number: 24659403
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Kanazawa University
• Principal Investigator: KITA Kenji 金沢大学, がん進展制御研究所, 助手 (80625252)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 肺がん / 脳転移

Outline of Final Research Achievements

We transfected eGFP and luciferase genes into human cancer cell lines, including lung cancer cells, and established in vivo imaging model of brain metastasis (brain tumor) with these cells by intracranial inoculation. These cancer cells produced various angiogenesis-related molecules, but there was no correlation between tumorigenecity in the brain and angiogenesis-related molecules. In the in vivo imaging model, anti-VEGF antibody did not inhibit tumor progression of VEGF-high producing cancer cells. These results suggest that brain metastasis may be regulated multiple factors in addition to VEGF-induced angiogenesis.

Research Products

• [Journal Article] In vivo imaging models of bone and brain metastases and pleural carcinomatosis with a novel human EML4-ALK lung cancer cell line. (2015)
  • Author(s): Nanjo S, Yano S, et al.
  • Journal Title: Cancer Sci Volume: 106 Issue: 3 Pages: 244-52
  • DOI: 10.1111/cas.12600
  • NAID: 120005830611
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Combined therapy with mutant-selective EGFR inhibitor and Met kinase inhibitor for overcoming erlotinib resistance in EGFR-mutant lung cancer (2012)
  • Author(s): Nakagawa T
  • Journal Title: Mol Cancer Ther. Volume: 11 Issue: 10 Pages: 2149-2157
  • DOI: 10.1158/1535-7163.mct-12-0195
  • Peer Reviewed
• [Journal Article] Dual inhibition of met kinase and angiogenesis to overcome HGF-induced EGFR-TKI resistance in EGFR mutant lung cancer (2012)
  • Author(s): Takeuchi S, Wang W, Li Q, Yamada T, Kita K, Donev IS, Nakamura T, Matsumoto K, Shimizu E, Nishioka Y, Sone S, Nakagawa T, Uenaka T, Yano
  • Journal Title: Am J Pathol Volume: 181 Issue: 3 Pages: 1034-1043
  • DOI: 10.1016/j.ajpath.2012.05.023
  • Peer Reviewed
• [Journal Article] Hsp90 Inhibition Overcomes HGF Triggering Resistance to EGFR-TKIs in EGFR-Mutant Lung Cancer by Decreasing Client Protein Expression and Angiogenesis (2012)
  • Author(s): Koizumi H, Yamada T, Takeuchi S, Nakagawa T, Kita K, Nakamura T, Matsumoto K, Suda K, Mitsudomi T, and Yano S
  • Journal Title: Journal of Thoracic Oncology Volume: Vol. 7: no.7 Issue: 7 Pages: 1078-1085
  • DOI: 10.1097/jto.0b013e3182519a2c
  • Peer Reviewed
• [Journal Article] Paracrine receptor activation by microenvironment triggers bypass survival signals and ALK inhibitor resistance in EML4-ALK lung cancer cells (2012)
  • Author(s): Yamada, T.
  • Journal Title: Clin. Cancer Res. Volume: 18 Issue: 13 Pages: 3592-3602
  • DOI: 10.1158/1078-0432.ccr-11-2972
  • Peer Reviewed