Analysis of EMT in CTCs isolated by a size-based microfluidic device in breast cancer patients

Research Project

Project/Area Number	16K10487
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	General surgery
Research Institution	Research Institute for Clinical Oncology, Saitama Cancer Center
Principal Investigator	NAGAI SHIGENORI 埼玉県立がんセンター(臨床腫瘍研究所), 病院乳腺腫瘍内科, 副部長 (20458277)
Co-Investigator(Renkei-kenkyūsha)	Tozuka Katsunori
Research Collaborator	SUGANUMA masami
Project Period (FY)	2016-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000) Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords	末梢血循環腫瘍細胞 / 上皮・間葉転換 / 乳がん / がん転移 / サイズ分画法 / 乳癌 / 上皮間葉転換 / Liquid biopsy / 抗がん剤 / 治療効果
Outline of Final Research Achievements	To determine EMT-related CTCs, we used a size-based microfluidic device for early and metastatic breast cancer patients. We found that the size-based device is more effective to detect CTCs than CellSearch System, and can determine not only epithelial-type CTCs, but also mesenchymal-type CTCs and SET-positive CTCs, using antibodies-cocktails. We also succeeded to analyze mRNA expression in CTCs fraction using digital PCR. Our established CTC-detection method will provide new insights for treatment of breast cancer.
Academic Significance and Societal Importance of the Research Achievements	本手法の開発によって、上皮性CTCだけでなく、間葉系CTC及び、SET陽性CTCなど多様なCTC亜集団を高い感度と特異性で検出できること可能となった。SET陽性CTCの検出は、SET阻害剤を用いた新しい乳がん治療の可能性も示唆している。本研究成果により、乳がん患者の予後予測だけでなく、がん治療の効果予測、さらには、がん転移の機構解明に役立つと期待される。