期刊
ONCOTARGET
卷 7, 期 13, 页码 16948-16961出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.7659
关键词
ovarian cancer; breast cancer; high throughput; multicellular tumor spheroids; preclinical drug testing
资金
- Department of Materials Science and Engineering
- College of Engineering at the University of Michigan
- DOD OCRP Early Career Investigator Award [W81XWH-13-1-0134]
Multicellular tumor spheroids are powerful in vitro models to perform preclinical chemosensitivity assays. We compare different methodologies to generate tumor spheroids in terms of resultant spheroid morphology, cellular arrangement and chemosensitivity. We used two cancer cell lines (MCF7 and OVCAR8) to generate spheroids using i) hanging drop array plates; ii) liquid overlay on ultra-low attachment plates; iii) liquid overlay on ultra-low attachment plates with rotating mixing (nutator plates). Analysis of spheroid morphometry indicated that cellular compaction was increased in spheroids generated on nutator and hanging drop array plates. Collagen staining also indicated higher compaction and remodeling in tumor spheroids on nutator and hanging drop arrays compared to conventional liquid overlay. Consequently, spheroids generated on nutator or hanging drop plates had increased chemoresistance to cisplatin treatment (20-60% viability) compared to spheroids on ultra low attachment plates (10-20% viability). Lastly, we used a mathematical model to demonstrate minimal changes in oxygen and cisplatin diffusion within experimentally generated spheroids. Our results demonstrate that methods of tumor spheroid generation result in varied cellular arrangement and chemosensitivity.
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