Parathyroid hormone (PTH) peptides through the regulation of hyaluronan metabolism affect osteosarcoma cell migration.
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.
Berdiaki
Aikaterini
A
Department of Histology, Division of Morphology, School of Medicine, University of Crete, Heraklion, Greece.
Datsis
Georgios A
GA
Nikitovic
Dragana
D
Tsatsakis
Aristidis
A
Katonis
Pavlos
P
Karamanos
Nikos K
NK
Tzanakakis
George N
GN
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
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