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3D Multicellular Stem-Like Human Breast Tumor Spheroids Enhance Tumorigenicity of Orthotopic Xenografts in Athymic Nude Rat Model
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 ce...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199968/ https://www.ncbi.nlm.nih.gov/pubmed/34205080 http://dx.doi.org/10.3390/cancers13112784 |
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author | Mokhtari, Reza Bayat Qorri, Bessi Sambi, Manpreet Baluch, Narges Kumar, Sushil Das, Bikul Szewczuk, Myron R. Yeger, Herman Cheng, Hai-Ling Margaret |
author_facet | Mokhtari, Reza Bayat Qorri, Bessi Sambi, Manpreet Baluch, Narges Kumar, Sushil Das, Bikul Szewczuk, Myron R. Yeger, Herman Cheng, Hai-Ling Margaret |
author_sort | Mokhtari, Reza Bayat |
collection | PubMed |
description | 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. ABSTRACT: 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. |
format | Online Article Text |
id | pubmed-8199968 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-81999682021-06-14 3D Multicellular Stem-Like Human Breast Tumor Spheroids Enhance Tumorigenicity of Orthotopic Xenografts in Athymic Nude Rat Model Mokhtari, Reza Bayat Qorri, Bessi Sambi, Manpreet Baluch, Narges Kumar, Sushil Das, Bikul Szewczuk, Myron R. Yeger, Herman Cheng, Hai-Ling Margaret Cancers (Basel) Article 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. ABSTRACT: 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. MDPI 2021-06-03 /pmc/articles/PMC8199968/ /pubmed/34205080 http://dx.doi.org/10.3390/cancers13112784 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Mokhtari, Reza Bayat Qorri, Bessi Sambi, Manpreet Baluch, Narges Kumar, Sushil Das, Bikul Szewczuk, Myron R. Yeger, Herman Cheng, Hai-Ling Margaret 3D Multicellular Stem-Like Human Breast Tumor Spheroids Enhance Tumorigenicity of Orthotopic Xenografts in Athymic Nude Rat Model |
title | 3D Multicellular Stem-Like Human Breast Tumor Spheroids Enhance Tumorigenicity of Orthotopic Xenografts in Athymic Nude Rat Model |
title_full | 3D Multicellular Stem-Like Human Breast Tumor Spheroids Enhance Tumorigenicity of Orthotopic Xenografts in Athymic Nude Rat Model |
title_fullStr | 3D Multicellular Stem-Like Human Breast Tumor Spheroids Enhance Tumorigenicity of Orthotopic Xenografts in Athymic Nude Rat Model |
title_full_unstemmed | 3D Multicellular Stem-Like Human Breast Tumor Spheroids Enhance Tumorigenicity of Orthotopic Xenografts in Athymic Nude Rat Model |
title_short | 3D Multicellular Stem-Like Human Breast Tumor Spheroids Enhance Tumorigenicity of Orthotopic Xenografts in Athymic Nude Rat Model |
title_sort | 3d multicellular stem-like human breast tumor spheroids enhance tumorigenicity of orthotopic xenografts in athymic nude rat model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199968/ https://www.ncbi.nlm.nih.gov/pubmed/34205080 http://dx.doi.org/10.3390/cancers13112784 |
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