RAW 264.7 Macrophage Polarization by Pancreatic Cancer Cells - A Model for Studying Tumour-promoting Macrophages

Anticancer Res. 2019 Jun;39(6):2871-2882. doi: 10.21873/anticanres.13416.

Abstract

Background/aim: Tumour-associated macrophages (TAMs) are highjacked M2-polarized macrophages that especially promote pancreatic cancer growth. The aim of this study was to identify an easy-to-use cell culture model suitable for studying this interaction and macrophage polarization.

Materials and methods: Co-cultures of two cell lines, PDA6606 cells with RAW macrophages cells were used in vitro and in ovo. Macrophages were analyzed by microscopy, magnetic resonance imaging (MRI), and flow cytometry.

Results: By comparing chemically-induced M1 and M2 macrophages, a clear induction of the M2 phenotype of RAW macrophages by PDA6606 pancreatic cancer cells was observed in vitro. In ovo, PDA6606 cells and conditioned media polarized macrophages to the M2 phenotype, which in turn promoted tumour growth and angiogenesis via their surface marker profiles and VEGF production.

Conclusion: PDA6606 pancreatic cancer cells expectantly and potently induced M2 polarization of RAW264.7 macrophages. This model may be used to study pancreatic cancer-macrophage plasticity in e.g. drug research in vitro and in ovo.

Keywords: Angiogenesis; M2 macrophages; VEGF; tumour-associated macrophages.

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Polarity
  • Cell Proliferation / drug effects
  • Coculture Techniques / methods*
  • Culture Media, Conditioned / pharmacology
  • Mice
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • RAW 264.7 Cells / cytology*
  • RAW 264.7 Cells / metabolism
  • Signal Transduction / drug effects
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Culture Media, Conditioned
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, mouse