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.
Highlights
Breast cancer is a very heterogeneous disease as evidenced by genetic and gene expression profiling studies[2] that further subclassify the above reported molecular subtypes
High levels of human telomerase reverse transcriptase (h-TERT) mRNA were observed in DHSF-BR16 and, as expected, in MCF-7 cells that are known to endogenously express this gene (Fig. 1A)
Both cell lines were highly sensitive to taxanes mainly to paclitaxel DHSFBR16 cells were more sensitive than MCF-7 cells (RI 0.34 for docetaxel and 0.31 for paclitaxel)
Summary
Breast cancer is a very heterogeneous disease as evidenced by genetic and gene expression profiling studies[2] that further subclassify the above reported molecular subtypes. At least 85% of H ER2+ overexpressing breast cancer is E R− and P R− at baseline[5], preventing patients from undergoing hormonal therapy On this basis, it is clear the need to identify new drugs as well as novel targets useful for the treatment of hormone receptor negative breast cancer. It is clear the need to identify new drugs as well as novel targets useful for the treatment of hormone receptor negative breast cancer It is well known the relevance of the complex interplay between cancer cells and tumor microenvironments in tumor response to treatment, in vitro studies based on established tumor cell lines still represent the starting point to design powerful in vivo and translational clinical studies[6]. We report the isolation and characterization of a spontaneously immortalized breast cancer cell line, a very rare phenomenon in primary breast cancer cultures, that shows human telomerase reverse transcriptase (h-TERT) expression levels similar to those of MCF-7 cell line, isolated in 1 97310 by a pleural effusion of breast cancer, and that represents a classical in vitro model for the study of breast cancer features, including sensitivity/ resistance to anticancer treatments
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