Advanced glycation endproducts-receptor interactions stimulate the growth of human pancreatic cancer cells through the induction of platelet-derived growth factor-B

Biochem Biophys Res Commun. 1996 May 24;222(3):700-5. doi: 10.1006/bbrc.1996.0807.


The molecular basis for the clinical association between diabetes mellitus and pancreatic cancer was investigated, using Mia PaCa-2 human pancreatic cancer cells in culture. Advanced glycation endproducts (AGE) prepared with bovine serum albumin and glucose were found to stimulate Mia PaCa-2 cell synthesis of DNA in a dose-dependent manner and also to significantly increase the number of viable cells. Evidence that platelet-derived growth factor-B (PDGF-B) mediates this growth promotion was obtained; AGE upregulated the level of PDGF-B mRNA, and antibodies against PDGF-BB completely neutralized the AGE-induced DNA synthesis. Antisense oligodeoxyribonucleotides complementary to mRNA encoding a receptor for AGE were found to reverse both the PDGF-B upregulation and the AGE-induced DNA synthesis. These results thus indicate that AGE ligand-receptor interactions could play an active part in the progression of pancreatic cancer through the induction of autocrine PDGF-B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Becaplermin
  • Cell Division / drug effects
  • Gene Expression
  • Glycation End Products, Advanced / pharmacology*
  • Humans
  • Molecular Sequence Data
  • Oligonucleotides, Antisense / pharmacology
  • Pancreatic Neoplasms / pathology*
  • Platelet-Derived Growth Factor / biosynthesis*
  • Platelet-Derived Growth Factor / genetics
  • Proto-Oncogene Proteins c-sis
  • RNA, Messenger / genetics
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / metabolism*
  • Tumor Cells, Cultured


  • Glycation End Products, Advanced
  • Oligonucleotides, Antisense
  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins c-sis
  • RNA, Messenger
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic
  • Becaplermin