Modulation of BDNF-TRKB Interactions on Schwann Cell-induced Oral Squamous Cell Carcinoma Dispersion In Vitro.

Abstract

Perineural invasion (PNI) is a significant pathological feature in head and neck cancer. The molecular mechanisms of PNI are poorly understood. Contrary to the previous belief that cancer cells invade nerves, recent studies have shown that Schwann cells (SC) can dedifferentiate, intercalate between cancer cells, and promote cancer dispersion. Communication between cells through brain-derived neurotrophic factor (BDNF) activation of its receptor tropomyosin receptor kinase B (TRKB) may contribute to these cellular events. We aimed to determine the effect of TRKB inhibitor ANA-12 on the direction of cell migration and degree of SC-induced oral cancer cell dispersion. Cell migration and dispersion assays were performed in vitro using murine SC and oral carcinoma cell lines. Assays were performed with and without ANA-12. Although SCs preferentially migrated towards cancer cells in control medium, there was minimal SC-associated cancer cell dispersion. In contrast, treatment with ANA-12 reduced migration of SCs and cancer cells towards each other and initiated more SC-associated cancer cell dispersion. This pilot study shows that BDNF-TRKB signaling may have a role in regulating interactions between SC and oral cancer cells that affect cell migration, intercalation, and cancer cell dispersion. Further research into these interactions may provide important clues about the molecular and cellular mechanisms of PNI.