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Journal article
Heterogeneous Breast Tumoroids: An In Vitro Assay for Investigating Cellular Heterogeneity and Drug Delivery
SLAS discovery : advancing life sciences R & D, Vol.12(1), pp.13-20
01 Feb 2007
PMID: 17166827
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Breast tumors are typically heterogeneous and contain diverse subpopulations of tumor cells with differing phenotypic properties. Planar cultures of cancer cell lines are not viable models of investigation of cell-cell and cell-matrix interactions during tumor development. This article presents an in vitro coculture-based 3-dimensional heterogeneous breast tumor model that can be used in drug resistance and drug delivery investigations. Breast cancer cell lines of different phenotypes (MDAMB231, MCF7, and ZR751) were cocultured in a rotating wall vessel bioreactor to form a large number of heterogeneous tumoroids in a single cell culture experiment. Cells in the rotating vessels were labeled with Cell Tracker fluorescent probes to allow for time course fluorescence microscopy to monitor cell aggregation. Histological sections of tumoroids were stained with hematoxylin and eosin, progesterone receptor, E-cadherin (E-cad), and proliferation marker ki67. In vitro tumoroids developed in this study recapture important features of the temporal-spatial organization of solid tumors, including the presence of necrotic areas at the center and higher levels of cell division at the tumor periphery. E-cad-positive MCF7 cells form larger tumoroids than E-cad-negative MDAMB231 cells. In heterogeneous tumors, the irregular surface roughness was mainly due to the presence of MDAMB231 cells, whereas MCF7 cells formed smooth surfaces. Moreover, when heterogeneous tumoroids were placed onto collagen gels, highly invasive MDAMB231 cell-rich surface regions produced extensions into the matrix, whereas poorly invasive MCF7 cells did not. The fact that one can form a large number of 1-mm tumoroids in 1 coculture attests to the potential use of this system at high-throughput investigations of cancer drug development and drug delivery into the tumor.
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Details
- Title
- Heterogeneous Breast Tumoroids: An In Vitro Assay for Investigating Cellular Heterogeneity and Drug Delivery
- Creators
- Alexandra P Vamvakidou - Drexel UniversityMark J Mondrinos - Drexel UniversitySokol P Petushi - Drexel UniversityFernando U Garcia - Drexel UniversityPeter I Lelkes - Drexel UniversityAydin Tozeren - Drexel University
- Publication Details
- SLAS discovery : advancing life sciences R & D, Vol.12(1), pp.13-20
- Publisher
- Sage
- Number of pages
- 8
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- [Retired Faculty]; Pathology (and Laboratory Medicine)
- Identifiers
- 991014878444204721
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- Biochemical Research Methods
- Biotechnology & Applied Microbiology
- Chemistry, Analytical