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Expression of functional toll like receptor 4 in estrogen receptor/progesterone receptor-negative breast cancer

Meliha Mehmeti1, Roni Allaoui2, Caroline Bergenfelz3

  • 1Center for Molecular Pathology, Department of Translational Medicine, Lund University, SUS Jan Waldenströmsgata 59, 20502, Malmö, Sweden. Meliha.Mehmeti@med.lu.se.

Breast Cancer Research : BCR
|September 23, 2015
PubMed
Abstract

Insights

Toll-like receptor 4 (TLR4) is functionally active in estrogen receptor/progesterone receptor-negative breast cancers, promoting pro-inflammatory genes and correlating with decreased survival. Targeting TLR4 may benefit this specific breast cancer subtype.

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Toll-like receptors (TLRs) are key pattern recognition receptors in innate immunity.
  • TLR activation by pathogen- or damage-associated molecular patterns (PAMPs/DAMPs) triggers pro-inflammatory gene transcription via NF-κB.
  • The role of TLRs in malignant cells, including breast cancer, remains largely unknown.

Purpose of the Study:

  • To investigate Toll-like receptor (TLR) and co-receptor expression patterns and function in breast cancer.
  • To determine the specific role of TLRs in different breast cancer subtypes, particularly estrogen receptor-positive (ER(+)) and estrogen receptor/progesterone receptor-negative (ER/PR-negative) cancers.

Main Methods:

  • Utilized real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) for TLR expression analysis.
  • Examined TLR expression in breast cancer cell lines (ER(+) and ER/PR-negative) and a cohort of 144 primary breast cancer samples.
  • Conducted in vitro assays including PAMP/DAMP stimulation, downstream signaling analysis, and TLR-silencing experiments to assess TLR function.

Main Results:

  • Toll-like receptor 4 (TLR4) was found to be expressed in a biologically active form, responding to PAMPs and DAMPs predominantly in ER/PR-negative breast cancers.
  • In vitro stimulation of TLR2 and TLR4 induced pro-inflammatory gene expression.
  • A strong correlation was observed between TLR4 expression and pro-inflammatory mediators in primary breast cancers, with TLR4 protein expression linked to decreased patient survival.

Conclusions:

  • Toll-like receptor 4 (TLR4) is expressed and functional in estrogen receptor/progesterone receptor-negative breast cancers.
  • The findings indicate that TLR4 plays a significant role in the progression and potentially the immune microenvironment of ER/PR-negative breast cancers.
  • Future therapeutic strategies targeting TLR4 should specifically focus on ER/PR-negative breast cancer patients.

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