S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Biomedical Sciences (대학원 의과학과) Theses (Ph.D. / Sc.D._의과학과)
Identification of viable cell populations in docetaxel-treated breast tumors using ferritin-based magnetic resonance imaging
유방암의 도세탁셀 치료 후 페리틴 자기공명영상을 이용한 생존 세포 집단의 동정
- 의과대학 의과학과
- Issue Date
- 서울대학교 대학원
- Human breast cancer stem cell; Ferritin; Chemotherapy; Reporter gene; Magnetic resonance imaging
- 학위논문 (박사)-- 서울대학교 대학원 : 의과학과, 2014. 2. 문우경.
- Introduction: Cancer stem cells (CSCs) are highly tumorigenic and are responsible for tumor progression and chemoresistance. Noninvasive imaging methods for the visualization of CSC populations within tumors in vivo will have a considerable impact on the development of new CSC-targeting therapeutics.
Methods: In this study, human breast cancer stem cells (BCSCs) transduced with dual reporter genes (human ferritin heavy chain [FTH] and enhanced green fluorescence protein [EGFP]) were transplanted into NOD/SCID mice to allow noninvasive tracking and quantification of BCSC-derived populations during docetaxel treatment.
Results: No changes in the properties of the BCSCs were observed due to ferritin overexpression. Magnetic resonance imaging (MRI) revealed significantly different signal intensities (R2* values) between BCSCs and FTH-BCSCs in vitro and in vivo. In addition, distinct populations of pixels with high R2* values were detected in docetaxel-treated FTH-BCSC tumors compared with control tumors, even before the tumor sizes changed. Histological analysis revealed that areas showing high R2* values in docetaxel-treated FTH-BCSC tumors by MRI contained EGFP+/FTH+ viable cell populations with high percentages of CD44+/CD24- cells.
Conclusions: These findings suggest that ferritin-based MRI, which provides high spatial resolution and tissue contrast, can be used as a reliable method to identify viable cell populations derived from BCSCs after chemotherapy and may serve as a new tool to monitor the efficacy of CSC-targeting therapies in vivo.