(271) Reciprocal interaction of Schwann cells and cancer facilitates neural invasion

Abstract

Neural invasion (NI) occurs in 85% of head and neck squamous cell carcinoma (HNSCC) cases and contributes to cancer pain. The cellular and molecular events that facilitate NI are poorly understood. Schwann cells play important roles in nerve protection, function, repair and regeneration. We propose that cancer cells and Schwann cells are attracted to each other, and cancer-induced impairment of Schwann cell function leads to nerve invasion by the cancer. We examined the reciprocal effect of Schwann cells and HNSCC on proliferation, migration, and invasion. A Schwann cell line (RSC96) and a HNSCC cell line (HSC-3) were used. Proliferation was examined using an automatic cell counter in a 6-well non-contact co-culture plate. RSC96 cells or HSC-3 cells were co-cultured for 24 or 48 hours; the varying number of the two respective cell types was used to determine the effect of the cell types on each other. Cell migration and invasion were studied using Transwell migration and invasion chambers. Migrated or invaded cells were stained using a Diff-Quick staining kit and counted using a Nikon Ti microscope. Schwann cells and cancer cells reciprocally promoted proliferation at low density or when cultured for a short duration (24 hour co-culture). High density or long duration (48 hour co-culture) reciprocally inhibited growth. The number of migrated or invaded HSC-3 cells increased when RSC96 cell number increased. RSC96 cells migrated towards HSC-3 cells in a cell number dependent manner. Our results indicate that Schwann cells and cancer cells bilaterally affect proliferation and migration. Long term exposure to cancer may dampen Schwann cells’ ability to proliferate which might ultimately lead to loss of nerve repair and nerve injury.