3D Multicellular Stem-Like Human Breast Tumor Spheroids Enhance Tumorigenicity of Orthotopic Xenografts in Athymic Nude Rat Model
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Lines
2.2. 2D Monolayer Cell Culture
2.3. Generation of 3D Multicellular Stem-Like Human Breast Tumor Spheroids
2.4. Methylcellulose Colony Formation Assay
2.5. Riboflavin Autofluorescence and HIF-2α Immunofluorescence Labeling
2.6. Flow Cytometry
2.7. AlamarBlue Cytotoxicity Assay
2.8. Trypan Blue Exclusion Viability Assay
2.9. Xenograft Animal Study
2.10. Magnetic Resonance Imaging (MRI)
2.11. Histology and Immunohistochemistry
2.12. Statistical Analysis
3. Results
3.1. Breast Cancer Cell Lines Form 3D Multicellular Spheroids on Agarose in Stem Cell Growth Factor Enriched Conditioned Medium after 3rd Generation Passage
3.2. Clonogenic Potential of Breast Cancer Cell Lines Forming 3D Multicellular Spheroids
3.3. Riboflavin Uptake in 3rd Generation 3D Breast Cancer Spheroids Confirms Stem Cell Characteristics
3.4. HIF-2α Expression in 3D Multicellular Stem-like Spheroids of MCF-7, ZR-75-1, and MDA-MB-231 Breast Cancer Cells
3.5. 3D Multicellular Stem-Like Spheroids of MCF-7, ZR-75-1, and MDA-MB-231 Breast Cancer Cells Express CD47, CD44, CD24, and CD133 Markers of Cancer Stem Cells
3.6. 3D Multicellular Stem-Like Spheroids of MCF-7, ZR-75-1, and MDA-MB-231 Breast Cancer Cells Display Increased Chemoresistance to Cisplatin
3.7. 3D Multicellular Stem-Like Breast Cancer Spheroids Co-Cultured with Human Fetal Lung Fibroblasts Successfully Establish Orthotopic Human Breast Tumors in Athymic Nude Rats with Increased Tumorigenicity
3.8. Characterization of Breast Cancer Cell Line-Derived Spheroid Xenografts in Athymic Nude Rats
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
bFGF | basic fibroblast growth factor |
BSA | bovine serum albumin |
CSC | cancer stem cell |
ECM | extracellular matrix |
EGF | epidermal growth factor |
EMT | epithelial-mesenchymal transition |
FBS | fetal bovine serum |
FLF | fetal lung fibroblasts |
MRI | magnetic resonance imaging |
PA | parental cell |
PBS | phosphate-buffered saline |
PBST | PBS-Tween |
PFA | paraformaldehyde |
SP | 3rd generation spheroid |
TME | tumor microenvironment |
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Mokhtari, R.B.; Qorri, B.; Sambi, M.; Baluch, N.; Kumar, S.; Das, B.; Szewczuk, M.R.; Yeger, H.; Cheng, H.-L.M. 3D Multicellular Stem-Like Human Breast Tumor Spheroids Enhance Tumorigenicity of Orthotopic Xenografts in Athymic Nude Rat Model. Cancers 2021, 13, 2784. https://doi.org/10.3390/cancers13112784
Mokhtari RB, Qorri B, Sambi M, Baluch N, Kumar S, Das B, Szewczuk MR, Yeger H, Cheng H-LM. 3D Multicellular Stem-Like Human Breast Tumor Spheroids Enhance Tumorigenicity of Orthotopic Xenografts in Athymic Nude Rat Model. Cancers. 2021; 13(11):2784. https://doi.org/10.3390/cancers13112784
Chicago/Turabian StyleMokhtari, Reza Bayat, Bessi Qorri, Manpreet Sambi, Narges Baluch, Sushil Kumar, Bikul Das, Myron R. Szewczuk, Herman Yeger, and Hai-Ling Margaret Cheng. 2021. "3D Multicellular Stem-Like Human Breast Tumor Spheroids Enhance Tumorigenicity of Orthotopic Xenografts in Athymic Nude Rat Model" Cancers 13, no. 11: 2784. https://doi.org/10.3390/cancers13112784