The Role of Receptors for Advanced Glycation End Product in Pancreatic Carcinogenesis

Abstract

Pancreatic cancer is the fourth-leading cause of cancer deaths worldwide that considered as the malignant tumor with the poorest prognosis and the lowest survival rate. This extremely violent disease is rarely diagnosed at an early level and difficult to treat due to its resistance to radiation therapy and chemotherapy. Here, we show that the receptor for advanced glycation end products (RAGE) and its ligands, advanced glycation end products (AGEs), high-mobility group box 1 (HMGB1) and S100 protein family are required for pancreatic cancer development, angiogenesis and metastasis through up-regulation of some anti-apoptotic molecules as matrix metalloproteinase -9 (MMP-9), kinase insert domain receptor (KDR), vascular endothelial growth factor (VEGF), platelet-derived growth factor-B (PDGF-B), hypoxia-inducible factor 1 (HIF1α), signal transducer and activator of transcription 3 (pSTAT3) and nuclear factor kappa B (NF-κB). In addition to the decrease in reactive oxygen species (ROS) those favouring the cancer cell growth and metastasis. The role of RAGE in pancreatic carcinogenesis needs further studies to investigate the relationship of RAGE with other anti-apoptotic and apoptotic molecules and examine the therapeutic potentials of anti-RAGE drugs for pancreatic cancer.

A high mannose concentration is well tolerated by colorectal adenocarcinoma and melanoma cells but toxic to normal human gingival fibroblast: an in vitro investigation

“…AGEs are collective name given to proteins, lipids and nucleic acids that undergo irreversible modification by reducing sugars or sugar-derived products [25]. It has been reported that the AGEs and AGE receptors interaction would stimulate the growth of human pancreatic cancer via the autocrine induction-derived growth factor-B [26]. Another study also reported that AGEs triggered the growth and migration of culture human melanoma cells [27].…”