Protumoral effect of macrophage through Axl activation on mucoepidermoid carcinoma

J Oral Pathol Med. 2014 Aug;43(7):538-44. doi: 10.1111/jop.12163.

Abstract

Objective: This study aims to test the potential involvement of Axl signaling in the protumoral effect of tumor-associated macrophages (TAMs) in mucoepidermoid carcinoma (MEC).

Materials and methods: We carried out cocultured experiments by incubation of MEC cells (UTMUC-1) and macrophages (THP-1) and examined Axl activation status. The expression of MMPs and behavior change were examined in UT-MUC-1 cells. The effect of Axl signaling on co-cultured cancer cells was further investigated by knockdown Axl expression and suppression by Axl-specific inhibitor R428.

Results: Activation of Axl signaling and increased expression and activity of MMP-2 and MMP-9 along with increased invasion/migration ability in MEC cells were observed when co-cultured with TAMs. Upon knockdown of Axl in MEC or addition of R428 in the co-cultured system, these co-cultured effects were diminished.

Conclusion: TAMs play a protumoral role in MEC via activation of the Axl signaling pathway, up-regulating MMPs expression, and increasing invasion/migration ability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Axl Receptor Tyrosine Kinase
  • Benzocycloheptenes / pharmacology
  • Carcinoma, Mucoepidermoid / enzymology*
  • Carcinoma, Mucoepidermoid / pathology
  • Cell Culture Techniques
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Coculture Techniques
  • Disease Progression
  • Enzyme Activation / physiology
  • Humans
  • Macrophage Activation / physiology
  • Macrophages / enzymology*
  • Matrix Metalloproteinase 2 / analysis
  • Matrix Metalloproteinase 9 / analysis
  • Neoplasm Invasiveness
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Proto-Oncogene Proteins / physiology*
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Signal Transduction / physiology*
  • Triazoles / pharmacology

Substances

  • Benzocycloheptenes
  • Proto-Oncogene Proteins
  • Triazoles
  • bemcentinib
  • Receptor Protein-Tyrosine Kinases
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • Axl Receptor Tyrosine Kinase
  • AXL protein, human