V3 versican isoform expression alters the phenotype of melanoma cells and their tumorigenic potential

Serra, Montserrat; Miquel, L.; Domenzain, Clelia; Docampo, María José; Fabra, Àngels; Wight, Thomas N.; Bassols, Anna

doi:10.1002/ijc.20813

Cited by 40 publications

(54 citation statements)

References 35 publications

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“…our previous study showed that the expression of the short isoform of versican, V3, in melanoma cells reversed the malignant phenotype, since V3-transduced cells resulted in a decrease in cell proliferation and an increase in cell adhesion to hyaluronan (11). Furthermore, our results showed that V3 overexpression reduced tumor growth rate in mice, but favored the appearance of secondary tumors (12).…”

Section: Introductionsupporting

confidence: 58%

“…MeWo human melanoma cells expressing the V3 isoform of versican (lV3Sn) and the empty control vector (lXSn) were obtained as previously described (11). The cells were cultured in dMeM medium supplemented with 10% fetal calf serum, 100 iu/ml penicillin and 100 µg/ml streptomycin (all from Gibco Brl/life Technologies, rockville, MD, USA) and grown in a humidified atmosphere at 37˚C with 5% co 2 .…”

Section: Methodsmentioning

confidence: 99%

“…The rneasy kit (Qiagen, Hilden, Germany) was used to isolate total rna from the cell cultures according to the manufacturer's protocol. The cultures were used at 144 h after seeding, as this is when the maximal difference in cell proliferation was observed (11). rna concentration and purity were measured using a nanodrop nd-1000 Spectrophotometer (nanodrop Technologies, Wilmington, de, uSa) and an rna labchip ® kit (agilent Technologies).…”

Section: Methodsmentioning

confidence: 99%

“…V3 overexpression in the MeWo melanoma cells decreased cell proliferation in vitro and in vivo, as previously described (11,12). To analyze whether ENG expression changed during …”

Section: Determination Of Differential Gene Expression Status Of Lv3smentioning

confidence: 99%

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Differential expression of endoglin in human melanoma cells expressing the V3 isoform of versican by microarray analysis

et al. 2010

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Abstract. Versican is a large chondroitin sulfate proteoglycan produced by several tumor types, including malignant melanoma, which exists as four different splice variants. The large isoforms V0 and V1 promote melanoma cell proliferation. We previously described that overexpression of the short V3 isoform in MeWo human melanoma cells markedly reduced tumor cell growth in vitro and in vivo, but favored the appearance of secondary tumors. This study aimed to elucidate the mechanisms of V3 by identifying differentially expressed genes between parental and V3-expressing MeWo melanoma cells using microarray analysis. V3 expression significantly reduced the expression of endoglin, a transforming growth factor-β superfamily co-receptor. other differentially expressed genes were VEGF and PPP1R14B. changes in endoglin levels were validated by qrT-Pcr and Western blotting.

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Section: Introductionsupporting

confidence: 58%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…V3 overexpression in the MeWo melanoma cells decreased cell proliferation in vitro and in vivo, as previously described (11,12). To analyze whether ENG expression changed during …”

Section: Determination Of Differential Gene Expression Status Of Lv3smentioning

confidence: 99%

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Differential expression of endoglin in human melanoma cells expressing the V3 isoform of versican by microarray analysis

et al. 2010

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“…GAG-b domains somehow interfere with the G3/EGFR interaction and decrease the antiproliferative effect of G3 in melanoma cells (Serra et al, 2005). We speculate that blockage of this interference by a GAG-b domain-specific antibody in our migration assays probably induced adhesion and consecutively decreased the migration of glioma cells.…”

Section: Discussionmentioning

confidence: 79%

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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Versican V1 isoform regulates cell‐associated matrix formation and cell behavior differentially from aggrecan in Swarm rat chondrosarcoma cells

Wasa

Nishida

Shinomura

et al. 2011

Intl Journal of Cancer

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Versican, a large chondroitin sulfate proteoglycan that binds hyaluronan and is composed of large extracellular matrix aggregates, has been shown to correlate with tumor progression. No studies have examined the roles of versican in chondrosarcoma nor compared them to those of aggrecan. In clinical specimens of human chondromatous tumors, versican expression was significantly increased in malignant tumors, moreover, as the tumor grade increased. To clarify the roles of versican in chondrosarcoma, versican splicing variant 1, variant 3 or only GFP was stably transfected to Swarm rat chondrosarcoma cells with Trap-In System. Forced expression of versican V1 isoform in Swarm rat chondrosarcoma cells induced a marked increase of cell-associated matrix compared to V3-, GFP-transfected or RCS cells. Versican was immunolocalized in a fashion similar to that of hyaluronan and more diffusively than aggrecan. Anchor-dependent and -independent growth was not affected by versican isoform expression, whereas cell motility and migration were significantly enhanced by V1 isoform transfection. Tumors formed in vivo with V1-transfected cells exhibited more myxomatous area and included more spindle shaped cells. These results support the concept that versican has the capacity to form more extensive cell-associated matrix than aggrecan, and the prominent matrix formation alters the cell behavior of chondrosarcoma more aggressively. These observations suggest that versican expression may serve as a marker of tumor grade determination in chondrosarcoma and possibly help to decide on therapeutic targets in higher grades of chondrosarcoma.Versican/PG-M is a large chondroitin sulfate (CS) proteoglycan of the extracellular matrix (ECM) that was initially identified in cultured fibroblasts, 1 and its chicken homolog (called PG-M) was isolated from developing limb buds.2 The core protein of versican consists of N-and C-terminal globular domains (G1 and G3) and two CS attachment domains (CSa and CS-b). The G1 domain of versican binds hyaluronan and the G3 domain consists of lectin-like carbohydrate recognition domain and epidermal growth factor (EGF)-like and complement-binding protein-like domains. Versican is able to regulate many cellular processes including adhesion, proliferation, apoptosis, migration and invasion via the highly negatively charged chondroitin/dermatan sulfate side chains and by interactions of the G1 and G3 domains with other proteins.3,4 Alternative splicing of versican generates at least four isoforms named V0, V1, V2 and V3.5,6 V0 contains two alternatively spliced GAG attachment domains (CS-a and CS-b). In contrast, V1 comprises the CS-b domain only, whereas V2 contains only CS-a domain. The CS-a and CS-b domains are both absent in the V3 isoform. The V0 isoform is particularly prevalent during early embryonic development 7 but less well expressed in adult tissues.8 On the contrary, several pieces of information have become available assigning distinct functions to individual versican isoforms, V1, V2 and V3. The ...

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V3 versican isoform expression alters the phenotype of melanoma cells and their tumorigenic potential

Cited by 40 publications

References 35 publications

Differential expression of endoglin in human melanoma cells expressing the V3 isoform of versican by microarray analysis

Differential expression of endoglin in human melanoma cells expressing the V3 isoform of versican by microarray analysis

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

Versican V1 isoform regulates cell‐associated matrix formation and cell behavior differentially from aggrecan in Swarm rat chondrosarcoma cells

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