Advanced glycation endproducts-receptor interactions stimulate the growth of human pancreatic cancer cells through the induction of platelet-derived growth factor-B.
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.
Yamamoto
Y
Y
Department of Biochemistry, Kanazawa University School of Medicine, Japan.
Yamagishi
S
S
Hsu
C C
CC
Yamamoto
H
H
D001483:Base Sequence; D000077214:Becaplermin; D002455:Cell Division / Q000187:drug effects; D015870:Gene Expression; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000473:pathology*; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000235:genetics; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D017127:Glycation End Products, Advanced; D016376:Oligonucleotides, Antisense; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D000077214:Becaplermin