Macrophages of M1 phenotype have properties that influence lung cancer cell progression

Alexander Hedbrant1, Jonny Wijkander1, Tomas Seidal1

  • 1Department of Health Sciences, Karlstad University, 651 88, Karlstad, Sweden.

Insights

Stromal macrophages, particularly M1 phenotype, significantly influence metastasis-related proteins like urokinase-type plasminogen activator (uPA) and matrix metalloproteinases (MMP) in lung cancers. M1 macrophages exhibit dual roles, promoting and inhibiting tumor growth.

Area of Science:

  • Oncology
  • Immunology
  • Cell Biology

Background:

  • Stromal macrophages are implicated in cancer metastasis through protein expression, but their comparative role versus cancer cells in lung cancers remains unclear.
  • Key proteins involved in metastasis include urokinase-type plasminogen activator (uPA), its receptor uPAR, plasminogen activator inhibitor-1 (PAI-1), and matrix metalloproteinases (MMP-2, MMP-9).

Purpose of the Study:

  • To compare the expression of metastasis-associated genes (uPA, uPAR, PAI-1, MMP-2, MMP-9) in M1 and M2 macrophages versus small cell lung cancer (SCLC) and lung squamous cell carcinoma (SCC) cell lines.
  • To investigate the effects of macrophage-conditioned media on cancer cell gene expression and growth.
  • To analyze the in-situ presence of uPAR, MMP-2, and MMP-9 in lung cancer biopsies.

Main Methods:

  • Quantitative analysis of mRNA expression in M1/M2 macrophages and NCI-H520 (SCC) / NCI-H69 (SCLC) cell lines.
  • Treatment of cancer cell lines with conditioned media (CM) from M1 and M2 macrophages.
  • Immunohistochemical analysis of tumor biopsies for uPAR, MMP-2, and MMP-9 expression in stromal cells.

Main Results:

  • Macrophages, especially M1 phenotype, expressed significantly higher levels of uPA, uPAR, PAI-1, and MMP-9 mRNA compared to cancer cell lines.
  • M1 macrophage-conditioned media upregulated PAI-1 in both SCC and SCLC cells and inhibited their growth.
  • uPAR, MMP-2, and MMP-9 were detected in stromal cells, including macrophages, within SCC and SCLC biopsies.

Conclusions:

  • Stromal macrophages, particularly M1 phenotype, play a substantial role in expressing key proteins affecting metastasis in lung cancer.
  • M1 macrophages demonstrate a dual role, potentially promoting metastasis via PAI-1 upregulation and inhibiting tumor growth simultaneously.
  • These findings highlight the complex interplay between macrophages and cancer cells in SCLC and SCC progression.