Role of urokinase plasminogen activator and its receptor in metastasis and invasion of neuroblastoma

Gao, Ya; Ji, Zong-Zheng; Zhang, Xiansheng; Xu, Quan; Li, Gongcai; Guo, Zhengtuan; Zheng, Bin; Guo, Xinkui

doi:10.1016/j.jpedsurg.2004.06.011

Cited by 20 publications

(18 citation statements)

References 33 publications

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“…We found the receptors PDGFRA and uPAR (plasminogen activator urokinase receptor) to be upregulated in ATRA exposed Wilms tumor cells. Of note, overexpression of uPAR has been associated with longer survival in children with neuroblastoma (Li et al, 2004). Taken together, this combination of differentially expressed genes strongly hints at a connection between retinoic acid and other signaling systems in tumor progression, of which the SMAD/TGFb pathway may play the most prominent role.…”

Section: Smad/transforming Growth Factor-beta (Tgfb) Signalingmentioning

confidence: 81%

All-trans retinoic acid treatment of Wilms tumor cells reverses expression of genes associated with high risk and relapse in vivo

Zirn

Samans

Spangenberg³

et al. 2005

Oncogene

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Section: Smad/transforming Growth Factor-beta (Tgfb) Signalingmentioning

confidence: 81%

All-trans retinoic acid treatment of Wilms tumor cells reverses expression of genes associated with high risk and relapse in vivo

Zirn

Samans

Spangenberg³

et al. 2005

Oncogene

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“…It is involved in localizing and promoting cell-surface plasminogen activation, plasmin formation and localized degradation of the extracellular matrix. 42 Overexpression of UPAR has been found in many cancers 23,[43][44][45][46] including pancreatic cancer, and contributes to tumor invasion and metastasis. 24,25 Recent studies by Ellis and colleagues have shown that pancreatic metastatic disease is dependent upon the UPA/ UPAR system, and that system activation and subsequent metastases is (i) mediated by insulin growth factor-1, hepatocyte growth (Table I).…”

Section: Discussionmentioning

confidence: 99%

Accurate discrimination of pancreatic ductal adenocarcinoma and chronic pancreatitis using multimarker expression data and samples obtained by minimally invasive fine needle aspiration

Chen

Zheng

Robbins

et al. 2007

Intl Journal of Cancer

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To augment cytological diagnosis of pancreatic ductal adenocarcinoma (PDAC) in tissue samples obtained by minimally invasive endoscopic ultrasound-guided fine needle aspiration, we investigated whether a small set of molecular markers could accurately distinguish PDAC from chronic pancreatitis (CP). Expression levels of 29 genes were first determined by quantitative real-time RT-PCR in a training set of tissues in which the final diagnosis was PDAC (n 5 20) or CP (n 5 10). Using receiver operator characteristic curve analysis, we determined that the single gene with the highest diagnostic accuracy for discrimination of CP vs. PDAC in the training study was urokinase plasminogen activator receptor (UPAR; AUC value 5 0.895, 95% CI 5 0.728-0.976). In the set of test tissues (n 5 14), the accuracy of UPAR decreased to 79%. However, we observed that the addition of 6 genes (EPCAM2, MAL2, CEA5, CEA6, MSLN and TRIM29; referred to as the 6-gene classifier) to UPAR resulted in high accuracy in both training and testing sets. Excluding 3 samples (out of 44; 7%) for which results of the UPAR/6-gene classifier were ''undefined,'' the accuracy of the UPAR/6-gene classifier was 100% in training samples (n 5 29), 92% in 12 test samples (p 5 0.004 that results were randomly generated; p 5 0.046 that the UPAR/6-gene classifier was comparable to UPAR alone; v 2 test), 100% in 3 samples for which the initial cytological diagnosis was ''suspicious'' and 98% (40/41) overall. Our results provide evidence that molecular marker expression data can be used to augment cytological analysis. ' 2006 Wiley-Liss, Inc.Key words: chronic pancreatitis; pancreatic ductal adenocarcinoma; urokinase plasminogen activator receptor; diagnostic accuracy Although the incidence of pancreatic ductal adenocarcinoma (PDAC) is only 1-2% and relatively low compared to other cancers, nearly all patients die from PDAC within 1-2 years.

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“…After irradiation, uPA expression was increased in association with an increased migration. uPA was overexpressed in high-risk, unfavorable tumor of neuroblastoma and that overexpression was associated with the ability of invasion, metastasis and a prognosis for neuroblastoma (26). MMPs are important in creating and maintaining an environment that initiates and maintains growth of primary and metastatic tumors (27).…”

Section: Discussionmentioning

confidence: 99%

Response of neuroblastoma cells to ionizing radiation: Modulation of in vitro invasiveness and angiogenesis of human microvascular endothelial cells

Jadhav

Mohanam²

2006

Int J Oncol

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Abstract.Neuroblastomas are the most common extra-cranial tumors of childhood and well known for their heterogeneous clinical behavior associated with certain genetic aberrations. Radiation therapy is an important modality for the treatment of high-risk neuroblastomas. In this study, we investigated whether ionizing irradiation modulate the migration and invasiveness of human neuroblastoma cells and expression of proangiogenic molecules known to be involved in tumor progression and metastasis. Irradiation of neuroblastoma cells resulted in increased migration and invasion as measured by spheroid migration and matrigel invasion assay respectively. Zymographic analysis revealed an increase in enzyme activity of MMP-9 and uPA in conditioned medium of irradiated neuroblastoma cells compared with non-irradiated cells. An increase in VEGF levels was also found in lysates of irradiated neuroblastoma cells. The up-regulation of uPA, MMP-9 and VEGF transcripts was also confirmed by RT-PCR analysis. Next, we examined the irradiated tumor cell-mediated modulation of endothelial cell behavior. Conditioned media from irradiated neuroblastoma cells enhanced capillary-like structure formation of microvascular endothelial cells. In a coculture system, irradiation of neuroblastoma cells enhanced endothelial cell invasiveness through Matrigel matrix. Endothelial cells treated with irradiated tumor cell conditioned medium were also analyzed for expression of uPA, MMP-9 and VEGF and compared to cells treated with non-irradiated tumor cell conditioned medium. These findings suggest that the irradiation effects of tumor cells could influence endothelial angiogenesis present in non-irradiated fields.

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Role of urokinase plasminogen activator and its receptor in metastasis and invasion of neuroblastoma

Cited by 20 publications

References 33 publications

All-trans retinoic acid treatment of Wilms tumor cells reverses expression of genes associated with high risk and relapse in vivo

All-trans retinoic acid treatment of Wilms tumor cells reverses expression of genes associated with high risk and relapse in vivo

Accurate discrimination of pancreatic ductal adenocarcinoma and chronic pancreatitis using multimarker expression data and samples obtained by minimally invasive fine needle aspiration

Response of neuroblastoma cells to ionizing radiation: Modulation of in vitro invasiveness and angiogenesis of human microvascular endothelial cells

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