title: Parathyroid hormone (PTH) peptides through the regulation of hyaluronan metabolism affect osteosarcoma cell migration.
abstract: Parathyroid hormone (PTH) strongly stimulates hyaluronan (HA) synthesis and secretion of both normal and carcinogenic cells of the osteoblastic lineage and improves skeletal microarchitecture. HA, a glycosaminoglycan component of the extracellular matrix (ECM), is capable of transmitting ECM-derived signals to regulate cellular function. In this study, we investigated whether the changes of HA metabolism induced by PTH (1-34) and PTH (7-84) peptides in moderately MG-63 and well-differentiated Saos 2 osteosarcoma cell lines, are correlated to their migration capabilities. Our results demonstrate that intermittent PTH (1-34) treatment significantly (P < or = 0.01) supported the migration of MG-63 cells, increased their HA-synthase-2 (HAS2) expression (P < or = 0.001), and enhanced their high-molecular size HA deposition in the pericellular matrix. Both increased endogenous HA production (P < or = 0.01) and treatment with exogenous high-molecular weight HA (P < or = 0.05) correlated to a significant increase of MG-63 cell migration capacity. Transfection with siHAS2 showed that PTH (1-34), mainly through HAS2, enhanced HA and regulated MG-63 cell motility. Interestingly, continuous PTH (1-34) treatment stimulated both Saos 2 cell HAS2 (P < or = 0.001) and HAS1 (P < or = 0.001) isoform expression inhibited their HYAL2 expression (P < or = 0.001) and modestly (P < or = 0.05) enhanced their migration. Therefore, the PTH (1-34) administration mode appears to distinctly modulate the migratory responses of the MG-63 moderately and Saos 2 well-differentiated osteosarcoma cell lines. Conclusively, the obtained data suggest that there is a regulatory effect of PTH (1-34), in an administration mode-dependent manner, on HA metabolism that is essential for osteosarcoma cell migration.
authors.affiliation: Department of Histology, Division of Morphology, School of Medicine, University of Crete, Heraklion, Greece.
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Berdiaki
authors.forename: Georgios A
authors.initials: GA
authors.lastname: Datsis
authors.forename: Dragana
authors.initials: D
authors.lastname: Nikitovic
authors.forename: Aristidis
authors.initials: A
authors.lastname: Tsatsakis
authors.forename: Pavlos
authors.initials: P
authors.lastname: Katonis
authors.forename: Nikos K
authors.initials: NK
authors.lastname: Karamanos
authors.forename: George N
authors.initials: GN
authors.lastname: Tzanakakis
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000494:pharmacology
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D010281:Parathyroid Hormone; D034741:RNA, Small Interfering; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; C101754:HAS2 protein, human; D000076002:Hyaluronan Synthases