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Tumor Biology

, Volume 36, Issue 11, pp 8715–8725 | Cite as

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

  • Alexander Hedbrant
  • Jonny Wijkander
  • Tomas Seidal
  • Dick Delbro
  • Ann Erlandsson
Research Article

Abstract

Stromal macrophages of different phenotypes can contribute to the expression of proteins that affects metastasis such as urokinase-type plasminogen activator (uPA), its receptor uPAR, and plasminogen activator inhibitor-1 (PAI-1), but knowledge of how essential their contribution is in comparison to the cancer cells in small cell lung cancer (SCLC) and lung squamous cell carcinoma (SCC) is lacking. The expression of uPA, uPAR, and PAI-1 and of the matrix metalloproteinases (MMP)-2 and MMP-9 were studied in human macrophages of M1 and M2 phenotype and compared to a lung SCC (NCI-H520) and a SCLC (NCI-H69) cell line. Effects of treatment with conditioned media (CM) from M1 and M2 macrophages on the expression of these genes in H520 and H69 cells as well as effects on the cell growth were investigated. In addition, data on the stromal macrophages immunoreactivity of uPAR, MMP-2, and MMP-9 in a few SCC and SCLC biopsies was included. uPAR, MMP-2, and MMP-9 were confirmed in stromal cells including macrophages in the SCC and SCLC biopsies. In vitro, both macrophage phenotypes expressed considerably higher mRNA levels of uPA, uPAR, PAI-1, and MMP-9 compared to the cancer cell lines, and regarding uPAR, the highest level was found in the M1 macrophage phenotype. Furthermore, M1 CM treatment not only induced an upregulation of PAI-1 in both H520 and H69 cells but also inhibited cell growth in both cell lines, giving M1 macrophages both tumor-promoting and tumor-killing potential.

Keywords

M1 macrophages M2 macrophages MMP Lung cancer uPA uPAR 

Notes

Acknowledgments

The present study was supported financially by the County Council of Värmland. Örebro University is gratefully acknowledged for financial support to D.D.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Alexander Hedbrant
    • 1
  • Jonny Wijkander
    • 1
  • Tomas Seidal
    • 1
  • Dick Delbro
    • 2
  • Ann Erlandsson
    • 1
  1. 1.Department of Health SciencesKarlstad UniversityKarlstadSweden
  2. 2.School of Health and Medical ScienceÖrebro UniversityÖrebroSweden

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