Inhibition of tropomyosine receptor kinase B on the migration of human Schwann cell and dispersion of oral tongue squamous cell carcinoma in vitro

Head Neck. 2019 Dec;41(12):4069-4075. doi: 10.1002/hed.25956. Epub 2019 Sep 9.

Abstract

Background: Schwann cells (SC) may play an important role in perineural invasion (PNI) by promoting cancer cell dispersion. Brain-derived neurotrophic factor (BDNF) may contribute to these cellular events by activating tropomyosine receptor kinase B (TrkB). This study examines the effect of TrkB inhibition on SC migration and oral cancer cell dispersion in vitro.

Methods: Human tongue squamous cell carcinoma (SCC-9) and human SCs were cocultured in three different conditioned mediums: control, BDNF, and TrkB inhibitor. Cell migration, cancer cell dispersion, and SC dedifferentiation were measured on time-lapse and immunofluorescence images.

Results: Cancer cell migration exceeded SC migration in all conditions. TrkB inhibition promoted SC dedifferentiation and significantly increased SC migration, when compared to BDNF conditions. TrkB inhibition also reduced cancer cell dispersion, when compared to control and BDNF-treated cultures.

Conclusion: SCs may have importance in the pathophysiology of PNI. TrkB inhibition may be a potential avenue for therapeutic intervention.

Keywords: BDNF; Schwann cells; TrkB; oral cancer; perineural invasion.

MeSH terms

  • Azepines / administration & dosage
  • Benzamides / administration & dosage
  • Brain-Derived Neurotrophic Factor / metabolism
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Cell Dedifferentiation / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Coculture Techniques
  • Humans
  • Membrane Glycoproteins / antagonists & inhibitors*
  • Membrane Glycoproteins / metabolism
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology
  • Neoplasm Invasiveness / pathology
  • Receptor, trkB / antagonists & inhibitors*
  • Receptor, trkB / metabolism
  • Schwann Cells / metabolism*
  • Tongue Neoplasms / metabolism
  • Tongue Neoplasms / pathology*

Substances

  • ANA 12 compound
  • Azepines
  • Benzamides
  • Brain-Derived Neurotrophic Factor
  • Membrane Glycoproteins
  • BDNF protein, human
  • Receptor, trkB
  • tropomyosin-related kinase-B, human