Breast cancer cell–neutrophil interactions enhance neutrophil survival and pro-tumorigenic activities

Lingyun Wu, Sugandha Saxena, Paran Goel, Dipakkumar R. Prajapati, Cheng Wang, Rakesh K. Singh

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Breast cancer remains the most prevalent cancer in women with limited treatment options for patients suffering from therapy-resistance and metastatic disease. Neutrophils play an important role in breast cancer progression and metastasis. We examined the pro-tumorigenic nature of the breast cancer cell–neutrophil interactions and delineated the differences in neutrophil properties between the chemotherapy-resistant and the parent tumor microenvironment. Our data demonstrated that high neutrophil infiltration is associated with disease aggressiveness and therapy resistance. In the human breast cancer dataset, expression of neutrophil-related signature gene expression was higher in tumors from therapy-resistant patients than therapy-sensitive patients. We observed that breast cancer-derived factors significantly enhanced neutrophil survival, polarization, and pro-inflammatory cytokine expression. Breast cancer cell-derived supernatant treated neutrophils significantly expressed high levels of interleukin-1β (IL-1β), CC-chemokine ligand-2-4 (CCL2, CCL3, CCL4), inducible nitric oxide synthase (iNOS), and matrix metallopeptidase-9 (MMP9), and formed extracellular traps (NETs). Moreover, neutrophils showed increased secretion of MMP9 when cultured with the supernatant of chemotherapy-resistant Cl66-Doxorubicin (Cl66-Dox) and Cl66-Paclitaxel (Cl66-Pac) cells in comparison with the supernatant of Cl66-parent cells. Together, these data suggest an important role of breast cancer cell–neutrophil interactions in regulating pro-tumor characteristics in neutrophils and its modulation by therapy resistance.

Original languageEnglish (US)
Article number2884
Pages (from-to)1-18
Number of pages18
JournalCancers
Volume12
Issue number10
DOIs
StatePublished - Oct 2020

Keywords

  • Breast cancer
  • Chemotherapy resistance
  • Matrix metallopeptidase 9
  • Neutrophil extracellular traps
  • Neutrophils

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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