Neurotrophin receptor expression in human primary retinoblastomas and retinoblastoma cell lines

Stephan, Harald; Zakrzewski, Johannes L.; Bölöni, Réka; Grasemann, Corinna; Lohmann, Dietmar; Eggert, Angelika

doi:10.1002/pbc.21369

Cited by 18 publications

(16 citation statements)

References 28 publications

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“…A recent report suggested no detectable levels of TrkB in Y79 cells [24] , which is quite different from a previous report according to which Y79 cells not only express NGF, BDNF, NT-3, and p75, but also the corresponding high-affinity receptors TrkA, TrkB, and TrkC [23] . We found that TrkA as well as TrkB are expressed in SNUOTRb1 and Y79 retinoblastoma cells as evaluated by Western blotting and RT-PCR ( fig.…”

Section: Discussioncontrasting

confidence: 50%

“…Accordingly, it has also been suggested that neurotrophin-related signaling pathways could play a crucial role in the biology of retinal development and ret- inoblastoma [22][23][24]26] . In the present study, we demonstrated that the neurotrophin receptors TrkA and TrkB are differentially expressed in retinoblastoma, which is closely related to the differentiation of retinoblastoma cells.…”

Section: Discussionmentioning

confidence: 99%

“…1 c). As endogenous NGF is moderately expressed in retinoblastoma cell lines [23,24], the proliferative response to NGF could already be saturated under normal culture conditions. However, it is also possible that TrkA is primarily involved in NGFinduced differentiation of retinoblastoma cells as that of neuroblastoma cells [17,19] .…”

Section: Retinoblastoma Cells Express Trka and Trkb And Addition Of Nmentioning

confidence: 99%

“…The expression of TrkA induces cell growth arrest and differentiation of neuroblastoma cells, which is correlated with a good prognosis [19] , whereas TrkB mediates cell proliferation and resistance to chemotherapy and is of poor prognosis [20,21] . The expression of neurotrophin receptors has also been demonstrated in a retinoblastoma cell line and primary retinoblastomas [22][23][24] ; the role of neurotrophin receptors in the pathogenesis of retinoblastoma remains to be elucidated.…”

mentioning

confidence: 99%

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Neurotrophin Receptors TrkA and TrkB in Retinoblastoma Are Differentially Expressed Depending on Cellular Differentiation

Kim¹,

Kim²,

Kim³

et al. 2009

Tumor Biol

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Retinoblastoma is the most common primary intraocular malignancy in children. With the progression of retinoblastoma, retinoblastoma cells lose their ability to differentiate. Regardless of many attempts to identify prognostic factors in retinoblastoma, further investigation for prognostic factors of retinoblastoma progression is still required because of the lack of sensitivity and specificity of these prognostic factors in predicting disease progression. We demonstrated that the differential expression of the neurotrophin receptors TrkA and TrkB is closely related to the differentiation of retinoblastoma cells. While retinoblastoma cells expressed TrkA as well as TrkB, their growth rates were not influenced by the addition of nerve growth factor to the culture medium. In experimental animal models of retinoblastoma, TrkA expression was primarily detected in more differentiated areas with high nm23 immunoreactivity whereas TrkB expression was apparent in more proliferative areas with high Ki67 immunoreactivity. With retinoic-acid-induced differentiation of retinoblastoma cells, TrkA expression significantly increased whereas TrkB significantly decreased. The differential expression of TrkA and TrkB with differentiation of retinoblastoma cells was mediated by extracellular-signal-regulated kinase 1/2 activation, which was confirmed by immunocytochemistry of TrkA. Therefore, our results suggest that the differential expression of TrkA and TrkB could be valuable as a therapeutic target, for instance using specific inhibitors.

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Section: Discussioncontrasting

confidence: 50%

Section: Discussionmentioning

confidence: 99%

Section: Retinoblastoma Cells Express Trka and Trkb And Addition Of Nmentioning

confidence: 99%

mentioning

confidence: 99%

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Neurotrophin Receptors TrkA and TrkB in Retinoblastoma Are Differentially Expressed Depending on Cellular Differentiation

Kim¹,

Kim²,

Kim³

et al. 2009

Tumor Biol

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“…BDNF-mediated p-Akt was used as a marker for TrkB activation in SY5Y-TrkB cells, in which inhibition of Akt sensitizes to chemotherapy (Ho et al, 2002;Jaboin et al, 2002). We had shown earlier that the chosen concentration of K252a (100 nM) is sufficient to inhibit Trk phosphorylation in other model systems (Stephan et al, 2008). Following treatment with K252a, p-Akt was strongly reduced in BDNF-activated SY5Y-TrkB cells, and this could not be seen in neurotrophin-treated SY5Y cells without Galectin-1-mediated NB aggressiveness F Cimmino et al TrkB expression ( Figure 5).…”

Section: Discussionmentioning

confidence: 79%

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

et al. 2009

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Expression of Trk receptors is an important prognostic factor in neuroblastoma (NB) and other cancers. TrkB and its ligand brain-derived neurotrophic factor (BDNF) are preferentially expressed in NB with poor prognosis, conferring invasive and metastatic potential to the tumor cells as well as enhancing therapy resistance. Galectin-1 (Gal-1) has emerged as an interesting cancer target, as it is involved in modulating cell proliferation, cell death and cell migration, all of which are linked to cancer initiation and progression. We previously identified Gal-1 mRNA to be upregulated in patients with aggressive, relapsing NB and found that Gal-1 protein was upregulated in human SY5Y NB cells on activation of ectopically expressed TrkB (SY5Y-TrkB), but not TrkA (SY5Y-TrkA). Here, we report that Gal-1 mRNA levels positively correlated with TrkB expression and anticorrelated with TrkA expression in a cohort of 102 primary NB. Immunohistochemical analyses of 92 primary NB specimens revealed high Gal-1 expression in stromal septae and in neuroblasts. BDNF-mediated activation of TrkB enhanced invasiveness and migration in vitro, which could be impaired by transient transfection using Gal-1-specific siRNA or a neutralizing antibody directed against Gal-1. The addition of recombinant Gal-1 (rGal-1) in the absence of BDNF partially restored migration and invasive capacity. Using the Trk inhibitor K252a, we could show that the upregulation of Gal-1 protein strictly depended on activated TrkB. Our data suggest that targeting Gal-1 might be a promising strategy for the treatment of aggressive NB.

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Association between virological response and decline in hemoglobin concentration during pegylated interferon and ribavirin therapy in HCV genotype 1: another story

Dai

Huang

et al. 2011

Hepatology

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We read with interest the reviews by Ghouri et al. 1 and Martinez et al. 2 Ghouri et al. analyzed the association of nonalcoholic fatty liver disease (NAFLD) with cardiovascular disease (CVD) and concluded that although a diagnosis of NAFLD should prompt diabetes screening, it is insufficient for considering patients to be at high risk for CVD. Martinez et al. evaluated noninvasive methods for assessing liver fibrosis and recommended that those tests with the highest diagnostic accuracy be validated against liver biopsy to facilitate their implementation in clinical practice.We meta-analyzed prospective data regarding the natural history of NAFLD and studies assessing the diagnostic accuracy of noninvasive methods for liver disease severity against liver biopsy in NAFLD, and we reached the following conclusions 3 :1. The two NAFLD histological subtypes, simple steatosis (SS) and nonalcoholic steatohepatitis (NASH), have different risks of liver-related complications: SS progresses to cirrhosis in less than 5% of cases; NASH progresses to cirrhosis in 10% to 15% of cases over 10 years and in 25% to 30% of cases in the presence of advanced fibrosis. 2. NAFLD patients have a 1.44-to 2.05-fold higher rate of CVD (depending on whether the diagnosis is based on an aminotransferase elevation or radiological/histological criteria) than the general population; restricting the analysis to studies adjusting for metabolic syndrome did not change the risk. Importantly, CVD mortality did not differ among NAFLD histological subtypes. ; restricting the analysis to studies adjusting for metabolic syndrome did not change the risk. Whether the risk of diabetes differs among NAFLD histological subtypes remains unclear: in a communitybased study, the 13-year incidence of diabetes was 2.98-fold higher in NASH patients versus SS patients. 3According to our analysis, a diagnosis of NAFLD should prompt a thorough three-focus assessment of cardiovascular, metabolic, and liver-related risks (Table 1). 4 Liver-related risk assessment remains problematic because it requires liver histology. Three noninvasive methods have been extensively validated: enzyme-linked immunosorbent assay-detected cytokeratin 18 fragments (9 studies enrolling 856 participants) for the detection of NASH and the NAFLD fibrosis score (13 studies enrolling 3064 participants) and FibroScan (6 studies enrolling 563 participants) for the detection of advanced fibrosis. We believe that these methods should be promptly implemented in diagnostic algorithms to select patients for liver biopsy in routine clinical practice while we continue to search for the ideal noninvasive marker.

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Neurotrophin receptor expression in human primary retinoblastomas and retinoblastoma cell lines

Abstract: Our findings suggest a role for neurotrophin signaling in the biology of retinoblastoma. General Trk inhibitors are effective in decreasing growth rates of retinoblastoma cells in vitro, and should be evaluated in in vivo studies.

Cited by 18 publications

References 28 publications

Neurotrophin Receptors TrkA and TrkB in Retinoblastoma Are Differentially Expressed Depending on Cellular Differentiation

Neurotrophin Receptors TrkA and TrkB in Retinoblastoma Are Differentially Expressed Depending on Cellular Differentiation

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

Association between virological response and decline in hemoglobin concentration during pegylated interferon and ribavirin therapy in HCV genotype 1: another story

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