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IL-8 and MCP-1/CCL2 regulate proteolytic activity in triple negative inflammatory breast cancer a mechanism that

Hossam Taha Mohamed1, Eslam A El-Ghonaimy2, Mohamed El-Shinawi3

  • 1Department of Zoology, Faculty of Science, Cairo University, Giza 12613, Egypt; Faculty of Biotechnology, October University for Modern Sciences and Arts, Giza 12451, Egypt.

Toxicology and Applied Pharmacology
|June 9, 2020
PubMed

Insights

Targeting interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1/CCL2) may treat inflammatory breast cancer (IBC). These cytokines drive invasion and metastasis in triple-negative IBC by increasing cathepsin B (CTSB) expression.

Area of Science:

  • Oncology
  • Cancer Biology
  • Molecular Medicine

Background:

  • Inflammatory breast cancer (IBC) is an aggressive cancer with poor prognosis, often triple-negative (TN).
  • The tumor microenvironment in IBC features tumor-associated macrophages (TAMs) and overexpressed cysteine protease cathepsin B (CTSB).
  • TAMs in IBC secrete elevated levels of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1/CCL2).

Purpose of the Study:

  • To investigate the roles of IL-8 and MCP-1/CCL2 in modulating proteolytic activity and invasiveness in triple-negative breast cancer (TNBC).
  • To compare these effects in TN-IBC versus non-IBC cell lines.
  • To elucidate the underlying molecular mechanisms involving signaling pathways.

Main Methods:

  • Quantitative real-time PCR to assess cytokine expression in TN-IBC tissues.
  • Cell-based assays using TN-non-IBC (HCC70) and TN-IBC (SUM149) cell lines.
  • Treatment with IL-8, MCP-1/CCL2, and specific pathway inhibitors (Dasatinib for p-Src, U0126 for p-Erk1/2).

Main Results:

  • IL-8 and MCP-1/CCL2 were significantly overexpressed in TN-IBC tissues.
  • Both cytokines induced CTSB expression and activated p-Src and p-Erk1/2 signaling pathways in HCC70 and SUM149 cells.
  • Inhibitors of p-Src and p-Erk1/2 reduced invasion and CTSB expression, effects reversed by IL-8 and MCP-1/CCL2.

Conclusions:

  • IL-8 and MCP-1/CCL2 play critical roles in promoting invasion and metastasis in triple-negative inflammatory breast cancer.
  • These cytokines mediate their effects by inducing CTSB expression via p-Src and p-Erk1/2 signaling pathways.
  • Targeting IL-8, MCP-1/CCL2, and associated signaling molecules offers a potential therapeutic strategy for TN-IBC.
Keywords:
Cathepsin BDasatinibIL-8Inflammatory Breast CancerMCP-1/CCL2U0126

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