Plasma-derived exosomal pyruvate kinase isoenzyme type M2 accelerates the proliferation and motility of oesophageal squamous cell carcinoma cells

Exosomal pyruvate kinase isoenzyme type M2 (PKM2) has been found to play a key role in the progression of human hepatocarcinoma. However, exosomal PKM2 (especially plasma-derived exosomal PKM2), in patients with oesophageal squamous cell carcinoma (ESCC) has not been well defined. In the present study, plasma-derived exosomes were isolated from healthy controls and patients with ESCC, and identified by transmission electronic microscopy, western blotting, nano-flow cytometry, nanoparticle tracking and phagocytosis analysis; exosomal PKM2 was detected by western blotting and ELISA. In addition, changes in cellular proliferation and motility in recipient cells (Eca109) were assessed using Cell Counting Kit-8, colony formation, wound-healing and Transwell assays. The PKM2 content was higher in exosomes from patients with ESCC than in those from healthy donors. Furthermore, exosomes from patients with ESCC enhanced the proliferation and motility of ESCC cells in vitro. Notably, PKM2 was found to be transferred by exosomes, and was able to act by activating STAT3. To verify the association between PKM2 and STAT3, immunohistochemistry was employed to analyse the protein levels of PKM2 and pSTAT3(Tyr705). These data revealed that PKM2 and pSTAT3(Tyr705) were upregulated and associated with overall survival in patients with ESCC. Therefore, the present study highlights that exosomes from patients with ESCC enhance the migration and invasiveness of ESCC cells by transferring PKM2.