Galectin-1 is a major effector of TrkB-mediated neuroblastoma aggressiveness

Cimmino, Flora; Schulte, Johannes H.; Zollo, Massimo; Koster, Jan; Versteeg, Rogier; Iolascon, Achille; Eggert, Angelika; Schramm, Alexander

doi:10.1038/onc.2009.70

Cited by 58 publications

(55 citation statements)

References 33 publications

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“…BDNF promotes survival and proliferation of ovarian and breast cancer cells (Descamps et al 2001;Qiu et al 2006) and activates antiapoptotic pathways in lung adenocarcinomas (Perez-Pinera et al 2007). In neuroblastoma, BDNF and TrkB expression is associated with poor prognosis, increased invasiveness and metastatic potential, and enhanced therapy resistance (Cimmino et al 2009). Thus, TrkB inhibitors have been put forward as a potential anticancer therapy (Desmet and Peeper 2006;Ruggeri et al 1999).…”

Section: Discussionmentioning

confidence: 99%

BDNF and PDE4, but not the GRPR, Regulate Viability of Human Medulloblastoma Cells

et al. 2009

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Medulloblastoma is the most common brain tumor of childhood. Emerging molecular targets in medulloblastoma include neurotrophin and neuropeptide receptors. In the present study, we have examined the influence of brain-derived neurotrophic factor (BDNF)/TrkB receptor- and gastrin-releasing peptide receptor (GRPR)-mediated signaling on the viability of human medulloblastoma cells. The expression of TrkB and GRPR was confirmed by immunohistochemistry and mRNA for both BDNF and GRPR was detected by reverse transcriptase polymerase chain reaction in Daoy, D283, and ONS76 cells. Treatment with BDNF significantly inhibited the viability of Daoy and D283, but not ONS76 cells, measured with the MTT assay. Neither the GRPR agonists GRP and bombesin nor the GRPR antagonist RC-3095 affected cell viability. Because previous findings have indicated that the viability of glioma cells might be enhanced by GRP when combined with the cAMP phosphodiesterase-4 (PDE4) inhibitor rolipram, we also examined the effects of rolipram alone or combined with GRP on cell viability. Rolipram significantly reduced the viability of all three cell lines, and the inhibitory effect of rolipram in Daoy cells was not modified by cotreatment with GRP. The results suggest that BDNF/TrkB and PDE4, but not the GRPR, regulate the viability of medulloblastoma cells.

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Section: Discussionmentioning

confidence: 99%

BDNF and PDE4, but not the GRPR, Regulate Viability of Human Medulloblastoma Cells

et al. 2009

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“…After treatment for 72 h with CTD and NCTD at different concentrations, the metabolic activity of the treated samples was assessed as a surrogate marker for cell proliferation, using the 3-(4,5-dimethylthiazol-2-yl)-5-diphenyltetrazolium bromide (MTT; Sigma) assay, as previously described [39]. Each result is the mean ± standard deviation (SD) from six replicates, and each experiment was repeated at least three times.…”

Section: Cell Viability Assaymentioning

confidence: 99%

“…Extraction of proteins from cultured cells was followed by immunoblotting with the relevant antibodies, as described elsewhere [39]. Each experiment was repeated at least three times.…”

Section: Western Blottingmentioning

confidence: 99%

Norcantharidin impairs medulloblastoma growth by inhibition of Wnt/β-catenin signaling

Cimmino¹,

Scoppettuolo²,

Carotenuto³

et al. 2011

J Neurooncol

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Medulloblastoma is one of the leading causes of morbidity and mortality in pediatric cancer. Wnt-active tumors, an independent molecular subgroup in medulloblastoma, are characterized by a distinct pattern of genomic aberrations. We assessed the anticancer activity of cantharidin and norcantharidin against medulloblastoma, as cell lines in vitro and in athymic nude mice in vivo. Cantharidin and norcantharidin treatment impaired the growth of DAOY and UW228 medulloblastoma cells and promoted the loss of β-catenin activation and the β-catenin nuclearization linked to N-cadherin impairment in vitro. Intra-peritoneal administration of norcantharidin inhibited the growth of intra-cerebellum tumors in orthotopic xenograft nude mice. Analysis of the xenograft tissues revealed enhanced neuronal differentiation and reduced β-catenin expression. Our findings suggest that norcantharidin has potential therapeutic applications in the treatment of medulloblastoma as a result of its ability to cross the blood-brain barrier and its impairment of Wnt-β-catenin signaling.

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“…The role of Gal-1 in molecular mechanisms leading to cancer development has been analyzed in several tumors (11) but surprisingly never in the molecular pathogenesis of HCC. In particular, it is still unknown whether Gal-1 affects the invasive ability of HCC as previously shown in other malignant tumors (25)(26)(27).…”

Section: Introductionmentioning

confidence: 98%

“…Gal-1 is a multifunctional protein involved in various aspects of tumorigenesis (cell-extracellular matrix and cell-cell interactions, cell migration, angiogenesis, tumor-immune escape) and has been described as a promising cancer target (11)(12)(13). Gal-1 expression has been examined in several malignant tumors (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24), and its correlation with tumor invasiveness and lymph node metastasis was demonstrated in breast cancer (25), neuroblastoma (26), oral squamous cell carcinoma and lung adenocarcinoma (27). Although Kondoh et al (28) showed that the activation of LGALS1 gene expression in HCC results from promoter hypomethylation, data on Gal-1 protein expression in HCC and its correlation to clinicopathological parameters were not available.…”

Section: Introductionmentioning

confidence: 99%

Galectin-1 and Its Involvement in Hepatocellular Carcinoma Aggressiveness

Spano

Russo

Maso

et al. 2009

Mol Med

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Hepatocellular carcinoma is one of the most common cancers worldwide. Despite several efforts to elucidate hepatocellular carcinoma molecular pathogenesis, it is still not fully understood. To acquire further insights into the molecular mechanisms of hepatocellular carcinoma, we performed a systematic functional genomic approach on human HuH-7 and JHH-6 cells. The subsequent analysis of the differentially expressed genes in human specimens revealed a molecular signature of 11 genes from which we selected the LGALS1 gene, which was overexpressed in hepatocellular carcinoma. The expression analysis in humans of Galectin-1 (Gal-1), the protein encoded by LGALS1, showed a Gal-1 preferential accumulation in the stromal tissue around hepatocellular carcinoma tumors. Moreover, a significant association between increased expression of Gal-1 in hepatocellular carcinoma and the presence of metastasis was observed. Interestingly, Gal-1 overexpression resulted in an increase of cell migration and invasion. In conclusion, this study provides a portfolio of targets useful for future investigations into molecular marker-discovery studies on a large number of patients and functional assays. In addition, our data provide evidence that Gal-1 plays a role in hepatocellular carcinoma cell migration and invasion, and we suggest that further studies should be conducted to fully establish the role of Gal-1 in hepatocellular carcinoma pathogenesis and evaluate Gal-1 as a potential molecular therapeutic target.

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Galectin-1 is a major effector of TrkB-mediated neuroblastoma aggressiveness

Cited by 58 publications

References 33 publications

BDNF and PDE4, but not the GRPR, Regulate Viability of Human Medulloblastoma Cells

BDNF and PDE4, but not the GRPR, Regulate Viability of Human Medulloblastoma Cells

Norcantharidin impairs medulloblastoma growth by inhibition of Wnt/β-catenin signaling

Galectin-1 and Its Involvement in Hepatocellular Carcinoma Aggressiveness

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