title: Platelet-derived growth factor BB mimics serum-induced dispersal of pancreatic epithelial cell clusters.
abstract: We showed previously that proliferating human islet-derived de-differentiated cells (DIDs) exhibit many characteristics of mesenchymal stem cells. Dispersed DIDs can be induced by serum deprivation to undergo mesenchymal-to-epithelial transition and aggregate into epithelial cell clusters (ECCs). Conversely, ECCs can be induced to disperse and undergo epithelial-to-mesenchymal transition (EMT) by re-addition of mammalian sera. In this study, we show that platelet-derived growth factor BB (PDGF-BB) mimics and mediates serum-induced ECCs' dispersal accompanied by accumulation of cytoplasmic β-catenin and a decrease in the levels of insulin and glucagon mRNAs. Moreover, we show that PDGF-BB-induced dispersal of ECCs is a more general phenomenon that occurs also with bone marrow mesenchymal stem cells (BM-MSCs) and dermal fibroblasts (DFs). In DIDs, BM-MSCs, and DFs, PDGF decreased the levels of DKK1 mRNA, suggesting involvement of the Wnt signaling pathway. PDGF-BB stimulated a significant increase in S473 phosphorylation of Akt and the PI3K specific inhibitor (PIP828) partially inhibited PDGF-BB-induced ECC dispersal. Lastly, the PDGF-receptor (PDGF-R) antagonist JNJ-10198409 inhibited both PDGF-BB--and serum-induced ECC dispersal. Epidermal growth factor (EGF), which shares most of the PDGF signaling pathway, did not induce dispersal and only weakly stimulated Akt phosphorylation. Our data suggest that PDGF-BB mediates serum-induced DIDs dispersal, correlated with the activation of the PI3K-Akt pathway.
authors.affiliation: Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Sahar
authors.initials: S
authors.lastname: Hiram-Bab
authors.forename: Liora S
authors.initials: LS
authors.lastname: Katz
authors.forename: Hagit
authors.initials: H
authors.lastname: Shapira
authors.forename: Judith
authors.initials: J
authors.lastname: Sandbank
authors.forename: Marvin C
authors.initials: MC
authors.lastname: Gershengorn
authors.forename: Yoram
authors.initials: Y
authors.lastname: Oron
mesh_terms: D000077214:Becaplermin; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D004847:Epithelial Cells / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000502:physiology*; D010179:Pancreas / Q000166:cytology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D000077214:Becaplermin; D051057:Proto-Oncogene Proteins c-akt