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

Sci Rep. 2021 Apr 16;11(1):8340. doi: 10.1038/s41598-021-87362-0.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / surgery
  • CD24 Antigen / genetics
  • CD24 Antigen / metabolism
  • Carcinoma, Ductal / drug therapy
  • Carcinoma, Ductal / genetics*
  • Carcinoma, Ductal / pathology*
  • Carcinoma, Ductal / surgery
  • Cell Line, Tumor
  • Cell Movement
  • Chemotherapy, Adjuvant
  • Epithelial Cell Adhesion Molecule / genetics
  • Epithelial Cell Adhesion Molecule / metabolism
  • Female
  • Humans
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / metabolism
  • Intracellular Membranes / metabolism
  • Keratin-7 / genetics
  • Keratin-7 / metabolism
  • Keratin-8 / genetics
  • Keratin-8 / metabolism
  • Neoadjuvant Therapy
  • Receptor, ErbB-2*
  • Receptors, Estrogen*
  • Receptors, Progesterone*
  • Spheroids, Cellular / pathology

Substances

  • CD24 Antigen
  • CD24 protein, human
  • CD44 protein, human
  • EPCAM protein, human
  • Epithelial Cell Adhesion Molecule
  • Hyaluronan Receptors
  • Keratin-7
  • Keratin-8
  • Receptors, Estrogen
  • Receptors, Progesterone
  • ERBB2 protein, human
  • Receptor, ErbB-2