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

Abstract

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.

Hypoxic microenvironment-induced exosomes confer temozolomide resistance in glioma through transfer of pyruvate kinase M2

“…The metabolic switch of liver nonparenchymal cells has been shown to be mediated by exosomal PKM2 in activated hepatic stellate cells [ 34 ]. Additionally, it was demonstrated that exosomal PKM2 transmitted in plasma reinforced growth and motility in esophageal squamous cell carcinoma cells [ 35 ]. In prostate carcinoma, bone metastases were found to be motivated by exosomal PKM2 transmission into bone stroma [ 36 ].…”

Extracellular Vesicles Are Important Mediators That Regulate Tumor Lymph Node Metastasis via the Immune System

“…Additionally, they are rarely present in blood circulation until tumor sizes increase to some degree; therefore, it is difficult to use these molecules for early diagnosis [ 132 , 134 , 135 ]. In fact, various studies indicate an association between EVs and diagnostic potential or prognosis prediction, so nucleic acids in EVs or membrane proteins on the surface of EVs might be novel biomarkers [ 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 ]. In this review, we have summarized that EVs mediate the immune evasion of tumors and induce tumor metastasis; below, we will show that EVs might be a diagnostic biomarker of tumor metastasis or an indicator of the immune response to tumors.…”

Biomaterial-enabled 3D cell culture technologies for extracellular vesicle manufacturing

“…1C), 104,125 which is linked with the production of EVs that contain increased levels of GAPDH, [126][127][128] and enolase. [129][130][131] Herein, we will discuss the current efforts in applying dynamic 3D culture for large scale EV production.…”