| Parathyroid hormone (PTH) peptides through the regulation of hyaluronan metabolism affect osteosarcoma cell migration. | |
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MedLine Citation:
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PMID: 20222016 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Aikaterini Berdiaki; Georgios A Datsis; Dragana Nikitovic; Aristidis Tsatsakis; Pavlos Katonis; Nikos K Karamanos; George N Tzanakakis |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: IUBMB life Volume: 62 ISSN: 1521-6551 ISO Abbreviation: IUBMB Life Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-04-21 Completed Date: 2010-07-13 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100888706 Medline TA: IUBMB Life Country: England |
Other Details:
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Languages: eng Pagination: 377-86 Citation Subset: IM |
Affiliation:
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Department of Histology, Division of Morphology, School of Medicine, University of Crete, Heraklion, Greece. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Antigens, CD44
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biosynthesis Cell Line, Tumor Cell Movement / drug effects* Glucuronosyltransferase / antagonists & inhibitors Humans Hyaluronic Acid / metabolism* Osteosarcoma / metabolism* Parathyroid Hormone / pharmacology* RNA, Small Interfering / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD44; 0/CD44 protein, human; 0/Parathyroid Hormone; 0/RNA, Small Interfering; 9004-61-9/Hyaluronic Acid; EC 2.4.1.-/HAS2 protein, human; EC 2.4.1.17/Glucuronosyltransferase |
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