3D Multicellular Stem-Like Human Breast Tumor Spheroids Enhance Tumorigenicity of Orthotopic Xenografts in Athymic Nude Rat Model
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Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON K7L 3N6, Canada
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Department of Experimental Therapeutics,Thoreau Laboratory for Global Health,M2D2, University of Massachusetts, Lowell, MA 01852, USA
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Department of Immunology and Allergy, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada
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QPS, Holdings LLC, Pencader Corporate Center, 110 Executive Drive, Newark, DE 19702, USA
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Department of Cancer and Stem Cell Biology, KaviKrishna Laboratory,GBP, Indian Institute of Technology, Guwahati 781039, India
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Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada
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The Edward S. Rogers Sr. Department of Electrical & Computer Engi-neering, Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5G 1M1, Canada
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Translational Biology & Engineering Program, Ted Rogers Centre for Heart Research, University of Toronto, Toronto, ON M5G 1M1, Canada
*
Authors to whom correspondence should be addressed.
Academic Editors: Maurizio Di Bonito, Michelino De Laurentiis and Monica Cantile
Cancers 2021, 13(11), 2784; https://doi.org/10.3390/cancers13112784
Received: 8 May 2021
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Revised: 21 May 2021
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Accepted: 28 May 2021
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Published: 3 June 2021
(This article belongs to the Special Issue Breast Cancer: Novel Histological and Molecular Markers for Diagnosis, Prognosis, Therapeutic Prediction, and Drug Resistance)
Simple Summary
Breast cancer presents a unique clinical problem because of the variety of cellular subtypes present, including cancer stem cells (CSCs). Breast CSCs can induce the formation of new blood vessels at the site of tumor growth and a develop metastatic phenotype by enhancing a stromal cell response, similar to that of the primary breast cancer. The aim of this study was to investigate breast cancer cells cultured in stromal stem cell factor-supplemented media to generate 3D spheroids that exhibit increased stem-like properties. These 3D stem-like spheroids reproducibly and efficiently established orthotopic breast cancer xenografts in the athymic nude rat. This approach enables a means to develop orthotopic tumors with a stem-like phenotype in a larger athymic rat rodent model of human breast cancer.
Therapeutic targeting of stem cells needs to be strategically developed to control tumor growth and prevent metastatic burden successfully. Breast cancer presents a unique clinical problem because of the variety of cellular subtypes present, including cancer stem cells (CSCs). The development of 3D stem-like properties of human breast tumor spheroids in stem cell factor conditioned media was investigated in orthotopic xenografts for enhanced tumorgenicity in the athymic nude rat model. MCF-7, ZR-75-1, and MDA-MB-231 breast cancer cell lines were cultured in serum-free, stem cell factor-supplemented medium under non-adherent conditions and passaged to generate 3rd generation spheroids. The spheroids were co-cultured with fetal lung fibroblast (FLF) cells before orthotopic heterotransplantation into the mammary fat pads of athymic nude rats. Excised xenografts were assessed histologically by H&E staining and immunohistochemistry for breast cancer marker (ERB1), proliferation marker (Ki67), mitotic marker (pHH3), hypoxia marker (HIF-2α), CSC markers (CD47, CD44, CD24, and CD133), and vascularization markers (CD31, CD34). Breast cancer cells cultured in stem cell factor supplemented medium generated 3D spheroids exhibited increased stem-like characteristics. The 3D stem-like spheroids co-cultured with FLF as supporting stroma reproducibly and efficiently established orthotopic breast cancer xenografts in the athymic nude rat.
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MDPI and ACS Style
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
AMA Style
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 B., Bessi Qorri, Manpreet Sambi, Narges Baluch, Sushil Kumar, Bikul Das, Myron R. Szewczuk, Herman Yeger, and Hai-Ling M. 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
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