Transforming Growth Factor-β as a key molecule triggering the expression of versican isoforms v0 and v1, Hyaluronan Synthase-2 and synthesis of Hyaluronan in Malignant Osteosarcoma cells

Nikitovic, Dragana; Zafiropoulos, Alexandros; Katonis, Pavlos; Tsatsakis, Aristidis; Theocharis, Achilleas D.; Karamanos, Nikos K.; Tzanakakis, George N.

doi:10.1080/15216540500531713

Cited by 57 publications

(41 citation statements)

References 42 publications

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“…The extracellular environment might become favourable for cell proliferation and survival when V1 expression is increased, as in the case of tissue development and tumour formation (Sheng et al, 2005). Recently, in parallel to our results in high-grade gliomas, TGF-b2 was reported to trigger the expression of V0/V1 and hyaluronan in osteosarcoma cells (Nikitovic et al, 2006).…”

Section: Discussionsupporting

confidence: 82%

The role of versican isoforms V0/V1 in glioma migration mediated by transforming growth factor-β2

et al. 2007

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Versican is a large chondroitin sulphate proteoglycan produced by several tumour cell types, including high-grade glioma. The increased expression of certain versican isoforms in the extracellular matrix (ECM) plays a role in tumour cell growth, adhesion and migration. Transforming growth factor-b2 (TGF-b2) is an important modulator of glioma invasion, partially by remodeling the ECM. However, it is unknown whether it interacts with versican during malignant progression of glioma cells. Here, we analysed the effect of TGF-b2 on the expression of versican isoforms. The expression of versican V0/V1 was upregulated by TGF-b2 detected by quantitative polymerase chain reaction and immunoprecipitation, whereas V2 was not induced. Using time-lapse scratch and spheroid migration assays, we observed that the glioma migration rate is significantly increased by exogenous TGF-b2 and inhibited by TGF-b2-specific antisense oligonucleotides. Interestingly, an antibody specific for the DPEAAE region of glycosaminoglycan-b domain of versican was able to reverse the effect of TGF-b2 on glioma migration in a dose-dependent manner. Taken together, we report here that TGF-b2 triggers the malignant phenotype of high-grade gliomas by induction of migration, and that this effect is, at least in part, mediated by versican V0/V1.

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Section: Discussionsupporting

confidence: 82%

The role of versican isoforms V0/V1 in glioma migration mediated by transforming growth factor-β2

et al. 2007

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“…Versican expression was normalized against a household gene (EEF1A1). 12,13,[16][17][18]20,23,34,[36][37][38][39] As the composition of the ECM influences the migration of inflammatory cells, 33 we have also measured the association between inflammatory cells and versican expression. Despite the reported production of versican isoforms V0 and V1 by human leukemic monocytes 40 and the reported …”

Section: Discussionmentioning

confidence: 99%

“…10 V0 and V1 are also the predominant isoforms found in cancer tissue. [11][12][13][14] Versican expression promotes tumor growth by destabilizing focal cell contacts, thus hampering cell adhesion and regulating angiogenesis. 10,15 Indeed, increased levels of versican have been reported in different tumor types such as adenocarcinomas, [16][17][18] squamous cell carcinomas, 19,20 sarcomas, 21 mesotheliomas 22 and malignant melanomas.…”

mentioning

confidence: 99%

Versican expression is associated with tumor-infiltrating CD8-positive T cells and infiltration depth in cervical cancer

et al. 2010

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Cervical carcinoma is the second most frequent cancer type in women worldwide. Both inflammatory cells and stromal cells are important for tumor progression. Stromal cells produce growth factors and extracellular matrix and provide an adequate environment for angiogenesis. Versican, a member of the extracellular matrix, has been shown to have a role in tumor progression. The aim of this study was to investigate versican expression, and its association with tumor-infiltrating inflammatory cell subsets and with clinicopathological parameters in human cervical cancers. We have studied the expression of versican in 149 cervical cancers using immunohistochemistry and mRNA in situ hybridization. Versican was predominantly expressed in the stroma (myofibroblasts). Using quantitative real-time-PCR, V0 was found to be the most prominent isoform. High stromal versican expression was significantly associated with a low number of tumor-infiltrating T cells (P ¼ 0.018) and particularly a low number of CD8-positive T cells (cytotoxic T cells; P ¼ 0.002). Stromal versican expression was significantly higher in patients with an infiltration depth 414 mm (P ¼ 0.004) and in patients with parametrial invasion (P ¼ 0.044). Stromal versican expression was not associated with survival. Our results suggest that versican expression in the stromal compartment of cervical cancers results in reduced numbers of intraepithelial CD8-positive T cells and enhanced local invasion.

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“…Contacts between the cells of the osteoblast lineage and surrounding ECM play a key role in the mechanisms that dictate cellular behavior (24). PTH, a powerful osteotropic agent, was established to have net anabolic effects on bone (2).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2010

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SummaryParathyroid 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 0.01) supported the migration of MG-63 cells, increased their HA-synthase-2 (HAS2) expression (P 0.001), and enhanced their high-molecular size HA deposition in the pericellular matrix. Both increased endogenous HA production (P 0.01) and treatment with exogenous high-molecular weight HA (P 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 0.001) and HAS1 (P 0.001) isoform expression inhibited their HYAL2 expression (P 0.001) and modestly (P 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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Transforming Growth Factor-β as a key molecule triggering the expression of versican isoforms v0 and v1, Hyaluronan Synthase-2 and synthesis of Hyaluronan in Malignant Osteosarcoma cells

Cited by 57 publications

References 42 publications

The role of versican isoforms V0/V1 in glioma migration mediated by transforming growth factor-β2

The role of versican isoforms V0/V1 in glioma migration mediated by transforming growth factor-β2

Versican expression is associated with tumor-infiltrating CD8-positive T cells and infiltration depth in cervical cancer

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

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