Background and Significance: Pancreatic cancer is a deadly disease with no targeted therapies and a five-year patient survival rate of 5-10%. Nerves are emerging drivers in tumorigenesis. Schwann cells support nerves and are a component of the neuronal microenvironment. They have also recently been found to be involved in pancreatic cancer progression. The aim of this study was to explore the Schwann cell secretome to identify proteins that stimulate pancreatic cancer cell growth and dissemination and thus could constitute new therapeutic targets.
Methodologies: Conditioned media isolated from human primary Schwann cell cultures was tested on pancreatic cancer cells proliferation (MTT assay), migration and invasion (trans-well) assay. Secretome profiling was performed on Schwann cell conditioned media with a triple quadrupole mass spectrometer (Orbitrap) coupled to liquid chromatography (LC-MS/MS) as part of a global proteomics approach. Only proteins with at least two unique peptides identified in high confidence were considered.
Major Findings: The Schwann cell secretome was found to stimulate the growth, migration and invasion of pancreatic cancer cells. Data-dependent acquisition/discovery (DDA) search resulted in the identification of 1187 secreted proteins with a confidence corresponding to a false discovery rate (FDR) <1%. 10 candidate proteins able to stimulate pancreatic cancer cell growth and invasion were validated by western blot and functional assays.
Conclusion: The secretome of Schwann cells contain proteins that can stimulate pancreatic cancer growth. These proteins constitute novel potential therapeutic targets whose clinical value should be further considered.