Exosomal Tenascin-c induces proliferation and invasion of pancreatic cancer cells by WNT signaling

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive gastrointestinal malignancies. PDAC has an unfavorable prognosis and a 5-year survival rate of less than 6%. Early diagnosis is difficult and the disease progresses rapidly. Local invasion and distant metastases are the underlying reasons for PDAC patient death. By exosome proteomic analysis of homologous cell lines, we identified several proteins that distinguished highly- from less-invasive pancreatic cancer cells in situ. The third most prominent protein, Tenascin-c (TNC), was chosen to assess effects on the malignant characteristics of pancreatic cancer cells. Silencing of TNC by short hairpin RNA (shRNA) in the cell lines PC-1.0 and Aspc-1 changed cellular proliferation, apoptosis, migration, and invasion. TNC expression was found to be positively related to proliferation and apoptosis, with each of these two processes reinforcing the other and regulated by the nuclear factor (NF)-κB pathway. TNC was found to promote PDAC cell line epithelial-mesenchymal transition by regulation of the Wnt/β-catenin pathway. This study demonstrated exosomal TNC to be closely associated with malignant features of pancreatic cancer cells including local invasion and distant metastasis. Hence, TNC is a potential therapeutic target for the treatment of PDAC invasiveness.