Establishment and characterization of a new spontaneously immortalized ER−/PR−/HER2+ human breast cancer cell line, DHSF-BR16

Abstract Invasive ductal carcinoma (IDC) constitutes the most frequent malignant cancer endangering women’s health. In this study, a new spontaneously immortalized breast cancer cell line, DHSF-BR16 cells, was isolated from the primary IDC of a 74-years old female patient, treated with neoadjuvant c...

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Autores principales:	Stefania Nobili, Antonella Mannini, Astrid Parenti, Chiara Raggi, Andrea Lapucci, Giovanna Chiorino, Sara Paccosi, Paola Di Gennaro, Vania Vezzosi, Paolo Romagnoli, Tommaso Susini, Marcella Coronnello
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/343a8a71c6f64f52a75d7ed4738556e0
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spelling	oai:doaj.org-article:343a8a71c6f64f52a75d7ed4738556e02021-12-02T14:31:01ZEstablishment and characterization of a new spontaneously immortalized ER−/PR−/HER2+ human breast cancer cell line, DHSF-BR1610.1038/s41598-021-87362-02045-2322https://doaj.org/article/343a8a71c6f64f52a75d7ed4738556e02021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87362-0https://doaj.org/toc/2045-2322Abstract Invasive ductal carcinoma (IDC) constitutes the most frequent malignant cancer endangering women’s health. In this study, a new spontaneously immortalized breast cancer cell line, DHSF-BR16 cells, was isolated from the primary IDC of a 74-years old female patient, treated with neoadjuvant chemotherapy and disease-free 5-years after adjuvant chemotherapy. Primary breast cancer tissue surgically removed was classified as ER−/PR−/HER2+, and the same phenotype was maintained by DHSF-BR16 cells. We examined DHSF-BR16 cell morphology and relevant biological and molecular markers, as well as their response to anticancer drugs commonly used for breast cancer treatment. MCF-7 cells were used for comparison purposes. The DHSF-BR16 cells showed the ability to form spheroids and migrate. Furthermore, DHSF-BR16 cells showed a mixed stemness phenotype (i.e. CD44+/CD24−/low), high levels of cytokeratin 7, moderate levels of cytokeratin 8 and 18, EpCAM and E-Cadh. Transcriptome analysis showed 2071 differentially expressed genes between DHSF-BR16 and MCF-7 cells (logFC > 2, p-adj < 0.01). Several genes were highly upregulated or downregulated in the new cell line (log2 scale fold change magnitude within − 9.6 to + 12.13). A spontaneous immortalization signature, mainly represented by extracellular exosomes-, plasma membrane- and endoplasmic reticulum membrane pathways (GO database) as well as by metabolic pathways (KEGG database) was observed in DHSF-BR16 cells. Also, these cells were more resistant to anthracyclines compared with MCF-7 cells. Overall, DHSF-BR16 cell line represents a relevant model useful to investigate cancer biology, to identify both novel prognostic and drug response predictive biomarkers as well as to assess new therapeutic strategies.Stefania NobiliAntonella ManniniAstrid ParentiChiara RaggiAndrea LapucciGiovanna ChiorinoSara PaccosiPaola Di GennaroVania VezzosiPaolo RomagnoliTommaso SusiniMarcella CoronnelloNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Stefania Nobili Antonella Mannini Astrid Parenti Chiara Raggi Andrea Lapucci Giovanna Chiorino Sara Paccosi Paola Di Gennaro Vania Vezzosi Paolo Romagnoli Tommaso Susini Marcella Coronnello Establishment and characterization of a new spontaneously immortalized ER−/PR−/HER2+ human breast cancer cell line, DHSF-BR16
description	Abstract Invasive ductal carcinoma (IDC) constitutes the most frequent malignant cancer endangering women’s health. In this study, a new spontaneously immortalized breast cancer cell line, DHSF-BR16 cells, was isolated from the primary IDC of a 74-years old female patient, treated with neoadjuvant chemotherapy and disease-free 5-years after adjuvant chemotherapy. Primary breast cancer tissue surgically removed was classified as ER−/PR−/HER2+, and the same phenotype was maintained by DHSF-BR16 cells. We examined DHSF-BR16 cell morphology and relevant biological and molecular markers, as well as their response to anticancer drugs commonly used for breast cancer treatment. MCF-7 cells were used for comparison purposes. The DHSF-BR16 cells showed the ability to form spheroids and migrate. Furthermore, DHSF-BR16 cells showed a mixed stemness phenotype (i.e. CD44+/CD24−/low), high levels of cytokeratin 7, moderate levels of cytokeratin 8 and 18, EpCAM and E-Cadh. Transcriptome analysis showed 2071 differentially expressed genes between DHSF-BR16 and MCF-7 cells (logFC > 2, p-adj < 0.01). Several genes were highly upregulated or downregulated in the new cell line (log2 scale fold change magnitude within − 9.6 to + 12.13). A spontaneous immortalization signature, mainly represented by extracellular exosomes-, plasma membrane- and endoplasmic reticulum membrane pathways (GO database) as well as by metabolic pathways (KEGG database) was observed in DHSF-BR16 cells. Also, these cells were more resistant to anthracyclines compared with MCF-7 cells. Overall, DHSF-BR16 cell line represents a relevant model useful to investigate cancer biology, to identify both novel prognostic and drug response predictive biomarkers as well as to assess new therapeutic strategies.
format	article
author	Stefania Nobili Antonella Mannini Astrid Parenti Chiara Raggi Andrea Lapucci Giovanna Chiorino Sara Paccosi Paola Di Gennaro Vania Vezzosi Paolo Romagnoli Tommaso Susini Marcella Coronnello
author_facet	Stefania Nobili Antonella Mannini Astrid Parenti Chiara Raggi Andrea Lapucci Giovanna Chiorino Sara Paccosi Paola Di Gennaro Vania Vezzosi Paolo Romagnoli Tommaso Susini Marcella Coronnello
author_sort	Stefania Nobili
title	Establishment and characterization of a new spontaneously immortalized ER−/PR−/HER2+ human breast cancer cell line, DHSF-BR16
title_short	Establishment and characterization of a new spontaneously immortalized ER−/PR−/HER2+ human breast cancer cell line, DHSF-BR16
title_full	Establishment and characterization of a new spontaneously immortalized ER−/PR−/HER2+ human breast cancer cell line, DHSF-BR16
title_fullStr	Establishment and characterization of a new spontaneously immortalized ER−/PR−/HER2+ human breast cancer cell line, DHSF-BR16
title_full_unstemmed	Establishment and characterization of a new spontaneously immortalized ER−/PR−/HER2+ human breast cancer cell line, DHSF-BR16
title_sort	establishment and characterization of a new spontaneously immortalized er−/pr−/her2+ human breast cancer cell line, dhsf-br16
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/343a8a71c6f64f52a75d7ed4738556e0
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Establishment and characterization of a new spontaneously immortalized ER−/PR−/HER2+ human breast cancer cell line, DHSF-BR16

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