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Cytokines secreted by stromal cells in TNBC microenvironment as potential targets for cancer therapy

Marie K Malone1, Karly Smrekar1, Sunju Park1

  • 1Department of Pharmaceutical Science, Albany College of Pharmacy and Health Science, Albany, NY, USA.

Cancer Biology & Therapy
|March 28, 2020
PubMed

Insights

Triple-negative breast cancer (TNBC) progression is driven by tumor microenvironment (TME) crosstalk. Targeting secreted factors like Lipocalin-2 (LCN2) shows promise for inhibiting TNBC growth and metastasis.

Area of Science:

  • Oncology
  • Cancer Biology
  • Immunology

Background:

  • Triple-negative breast cancer (TNBC) lacks targeted therapies, leading to poor prognosis and metastatic disease.
  • Tumor microenvironment (TME) crosstalk between cancer and stromal cells influences TNBC heterogeneity, growth, and metastasis.
  • Interleukin-6 (IL-6), IL-8, and CCL5 are previously implicated in TNBC progression.

Purpose of the Study:

  • To systematically analyze cytokine factors secreted by stromal components induced by TNBC cells.
  • To identify novel secreted factors involved in EMT, proliferation, metabolism, and matrisome pathways in TNBC.
  • To investigate the role of Lipocalin-2 (LCN2) in TNBC-stromal cell crosstalk and its therapeutic potential.

Main Methods:

  • Bioinformatic analysis of cytokine factors secreted from four stromal cell types (fibroblasts, macrophages, lymphatic endothelial cells, blood microvascular endothelial cells) induced by four TNBC cell types.
  • Selection of candidate secreted factors involved in key cancer pathways.
  • Validation of LCN2 secretion and assessment of LCN2 antibody efficacy on TNBC cell growth and migration.

Main Results:

  • Several secreted factors, including LCN2, GM-CSF, CST3, IL-6, IL-8, and CHI3L1, were identified as highly ranked candidates.
  • Lipocalin-2 (LCN2) was significantly upregulated in the crosstalk between stromal cells and TNBC cells.
  • Antibody-mediated inhibition of LCN2 demonstrated a reduction in TNBC cell growth and migration.

Conclusions:

  • Secreted factors, particularly LCN2, play a crucial role in TNBC progression through stromal component crosstalk.
  • Targeting these secreted factors represents a promising therapeutic strategy for TNBC.
  • LCN2 inhibition offers a potential avenue for treating metastatic TNBC by disrupting tumor-stromal interactions.
Keywords:
TNBCsecreted factorsstromal cellstumor microenvironmentsecretome

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