Comparative analysis of tumor spheroid generation techniques for differential in vitro drug toxicity

Shreya Raghavan, Pooja Mehta, Eric N. Horst, Maria R. Ward, Katelyn R. Rowley, Geeta Mehta

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)16948-16961
Number of pages14
JournalOncotarget
Volume7
Issue number13
DOIs
StatePublished - Mar 29 2016

Keywords

  • Breast cancer
  • High throughput
  • Multicellular tumor spheroids
  • Ovarian cancer
  • Preclinical drug testing

ASJC Scopus subject areas

  • Oncology

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