Parathyroid hormone (PTH) peptides through the regulation of hyaluronan metabolism affect osteosarcoma cell migration

Berdiaki, Aikaterini; Datsis, Georgios A.; Nikitovic, Dragana; Tsatsakis, Aristidis; Katonis, Pavlos; Karamanos, Nikos K.; Tzanakakis, George N.

doi:10.1002/iub.320

Cited by 23 publications

(27 citation statements)

References 27 publications

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“…FGF‐2 has previously been shown to affect osteoblast progenitor proliferation and apoptosis rates in a manner that is synergistic with PTH(1–34) action [4]. Our recent study demonstrated that PTH(1–34) modulates osteosarcoma cell migration [19]. In view of the fact that PTH(1–34) and FGF‐2 signaling collaborate to regulate bone cell growth, we hypothesized that FGF‐2 might also participate in PTH(1–34)‐dependent osteosarcoma cell migration.…”

Section: Resultsmentioning

confidence: 99%

Parathyroid hormone affects the fibroblast growth factor–proteoglycan signaling axis to regulate osteosarcoma cell migration

et al. 2011

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Parathyroid hormone (PTH)(1-34), which has been established to have a dual effect on bone metabolism, was recently found to regulate osteosarcoma cell migration. A significant part of the bone anabolic action of PTH(1-34) is attributed to fibroblast growth factor (FGF)-2 stimulation. Furthermore, it was recently suggested that the FGF-proteoglycan axis may form an extracellular matrix-related regulatory feedback loop that controls osteoblastic lineage cell proliferation and execution of the osteogenic program. In this study, we investigated the possible participation of FGF-2 signaling in PTH(1-34)-dependent osteosarcoma cell migration. FGF-2 treatment of osteosarcoma cells resulted in a significant increase (P £ 0.01) in MG63 cell migration, similar to that caused by PTH(1-34). mRNA expression analysis of cells treated with PTH(1-34) showed a strong increase in FGF-2 transcript levels (P = 0.0015). Interestingly, the addition of FGF-2 to MG63 cells led to significant downregulation of small leucine-rich proteoglycan biglycan expression at both the mRNA (P £ 0.0001) and protein (60%) levels. In order to examine the significance of biglycan on MG63 cell migration, transfection with short interfering RNA specific for biglycan was performed, resulting in a significant increase (P £ 0.01) in the migration capacity of biglycan-deficient MG63 cells. In contrast, exogenous human recombinant biglycan strongly inhibited the migration of these cells (P £ 0.01). Finally, a direct correlation between PTH(1-34) action and biglycan expression was established by the finding of a significant decrease (P £ 0.01) in biglycan transcript levels in PTH(1-34)-treated cells. To summarize, the present study demonstrates a novel cooperative mechanism of PTH(1-34) and FGF-2 action that results in specific alteration of the biglycan extracellular matrix content to regulate osteosarcoma cell migration.

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Section: Resultsmentioning

confidence: 99%

Parathyroid hormone affects the fibroblast growth factor–proteoglycan signaling axis to regulate osteosarcoma cell migration

et al. 2011

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“…PTHrP downregulated expression of proapoptotic Bax and PUMA and upregulated antiapoptotic Bcl-2 and Bcl-xl. Berdiaki et al [67], using MG-63 and SaOS-2 osteosarcoma cell lines, showed that PTH peptides enhanced osteosarcoma cell migration through the regulation of hyaluron metabolism. However, a previous study showed that overexpression of PTHrP in a murine osteoblastic osteosarcoma cell line reduced cell proliferation by 80% [68].…”

Section: Pathogenesismentioning

confidence: 99%

The Molecular Pathogenesis of Osteosarcoma: A Review

Broadhead

Clark

Myers

et al. 2011

Sarcoma

307

293

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Osteosarcoma is the most common primary malignancy of bone. It arises in bone during periods of rapid growth and primarily affects adolescents and young adults. The 5-year survival rate for osteosarcoma is 60%–70%, with no significant improvements in prognosis since the advent of multiagent chemotherapy. Diagnosis, staging, and surgical management of osteosarcoma remain focused on our anatomical understanding of the disease. As our knowledge of the molecular pathogenesis of osteosarcoma expands, potential therapeutic targets are being identified. A comprehensive understanding of these mechanisms is essential if we are to improve the prognosis of patients with osteosarcoma through tumour-targeted therapies. This paper will outline the pathogenic mechanisms of osteosarcoma oncogenesis and progression and will discuss some of the more frontline translational studies performed to date in search of novel, safer, and more targeted drugs for disease management.

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“…Parathyroid hormone (PTH), PTH peptides, as well as the PTH receptor (PTHR) have been shown by multiple reports to enhance OS cell migration and invasion (100, 101). Autocrine motility factor (AMF), a major cell motility-stimulating factor secreted by tumor cells, is associated with tumor metastasis in various human cancers including OS (102).…”

Section: Bone Sarcoma Tumorigenesismentioning

confidence: 99%

Understanding the Biology of Bone Sarcoma from Early Initiating Events through Late Events in Metastasis and Disease Progression

Zhu¹,

McManus²,

Hughes³

2013

Front. Oncol.

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The two most common primary bone malignancies, osteosarcoma (OS), and Ewing sarcoma (ES), are both aggressive, highly metastatic cancers that most often strike teens, though both can be found in younger children and adults. Despite distinct origins and pathogenesis, both diseases share several mechanisms of progression and metastasis, including neovascularization, invasion, anoikis resistance, chemoresistance, and evasion of the immune response. Some of these processes are well-studies in more common carcinoma models, and the observation from adult diseases may be readily applied to pediatric bone sarcomas. Neovascularization, which includes angiogenesis and vasculogenesis, is a clear example of a process that is likely to be similar between carcinomas and sarcomas, since the responding cells are the same in each case. Chemoresistance mechanisms also may be similar between other cancers and the bone sarcomas. Since OS and ES are mesenchymal in origin, the process of epithelial-to-mesenchymal transition is largely absent in bone sarcomas, necessitating different approaches to study progression and metastasis in these diseases. One process that is less well-studied in bone sarcomas is dormancy, which allows micrometastatic disease to remain viable but not growing in distant sites – typically the lungs – for months or years before renewing growth to become overt metastatic disease. By understanding the basic biology of these processes, novel therapeutic strategies may be developed that could improve survival in children with OS or ES.

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Parathyroid hormone (PTH) peptides through the regulation of hyaluronan metabolism affect osteosarcoma cell migration

Cited by 23 publications

References 27 publications

Parathyroid hormone affects the fibroblast growth factor–proteoglycan signaling axis to regulate osteosarcoma cell migration

Parathyroid hormone affects the fibroblast growth factor–proteoglycan signaling axis to regulate osteosarcoma cell migration

The Molecular Pathogenesis of Osteosarcoma: A Review

Understanding the Biology of Bone Sarcoma from Early Initiating Events through Late Events in Metastasis and Disease Progression

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