Prognostic value of intact and cleaved forms of the urokinase plasminogen activator receptor in a retrospective study of 518 colorectal cancer patients

Lomholt, Anne Fog; Christensen, Ib Jarle; Høyer‐Hansen, Gunilla; Nielsen, Hans Jørgen

doi:10.3109/0284186x.2010.491086

Cited by 49 publications

(43 citation statements)

References 21 publications

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“…This finding is in agreement with previous studies using different quantitative assay methods, including ELISA and mRNA expression analyses, showing that high levels of uPAR are associated with a poor prognosis in several tumour types, including breast, pulmonary and colorectal cancer. 8,12,[14][15][16] Following complete surgical resection of adenocarcinomas in oesophagus and the stomach, it has been reported that the total uPAR-content in tumour tissue extracts has a strong prognostic impact. 32,33 This is well in accordance with our findings (see Fig.…”

Section: Discussionmentioning

confidence: 99%

“…12,13 Several studies have shown that increased levels of uPAR is linked to poor prognosis in a number of cancers, including pulmonary carcinomas, colorectal and breast cancer. 8,[14][15][16] We recently reported that uPAR in gastric cancers is frequently expressed in cancer cell populations, 17 which are likely directly linked to the malignancy of the disseminated cancer cells in the bone marrow. 18 In this study, we examine uPAR expression in adenocarcinomas around the gastro-oesophageal junction and we address at which stage of malignant transformation and in which cell types uPAR is expressed, and to which extent this can give information on the clinical course.…”

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confidence: 99%

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Prognosis in adenocarcinomas of lower oesophagus, gastro‐oesophageal junction and cardia evaluated by uPAR‐immunohistochemistry

Lærum

Øvrebø

Skarstein

et al. 2011

Intl Journal of Cancer

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Adenocarcinomas of lower oesophagus, gastro‐oesophageal junction and cardia in humans are highly invasive tumours with poor prognosis. The localisation of urokinase‐type plasminogen activator receptor (uPAR) was determined in 66 patients; 60 with adenocarcinomas and six cases with Barrett's oesophagus. uPAR was expressed in nearly all cases of invasive adenocarcinomas by populations of cancer cells, macrophages and myofibroblasts at both the invasion front and the tumour core. In areas with high‐grade dysplasia or with Barrett's metaplasia adjacent to the tumour tissue, no uPAR‐immunoreactivity was found. High local expression of uPAR, therefore, appears to be a characteristic marker for invasive behaviour in this tumour, suggesting that uPAR's contribution to matrix degradation during invasive growth is a late event in carcinogenesis. Using a scoring system for semiquantitative estimation of uPAR‐positivity on immmunohistochemically stained specimens, a significant association was found between poor overall survival and high uPAR‐score for cancer cells in the tumour core and for macrophages peripherally at the tumour invasion zone. In multivariate analysis, these two uPAR‐scores were confirmed as highly significant prognostic parameters independent of Tumour, Node, Metastasis (TNM)‐stage and World Health Organization (WHO) classification. The proteolytic action of these malignant and nonmalignant accessory cells thus seemed to follow two main patterns: one dominated by uPAR positive cancer cells and one by uPAR‐positive macrophages. Scoring of uPAR‐positivity might be a useful parameter for onset of invasion and prognosis in these adenocarcinomas.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Prognosis in adenocarcinomas of lower oesophagus, gastro‐oesophageal junction and cardia evaluated by uPAR‐immunohistochemistry

Lærum

Øvrebø

Skarstein

et al. 2011

Intl Journal of Cancer

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“…SuPAR levels in plasma/serum were found to be elevated and predictive of progression in different types of cancer such as colorectal [11] and ovarian cancers [8] and multiple myeloma [17,24].…”

Section: Introductionmentioning

confidence: 99%

Elevated soluble urokinase receptor values in CSF, age and bacterial meningitis infection are independent and additive risk factors of fatal outcome

Tzanakaki

Paparoupa

Kyprianou

et al. 2011

Eur J Clin Microbiol Infect Dis

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The aim of the present study was to evaluate the potential role of cerebrospinal fluid soluble urokinase receptor (suPAR) level, infection and age as risk factors for fatal outcome in patients suspected of having meningitis and/or bacteraemia on admission to hospital. A total of 545 cerebrospinal fluid samples from patients with clinically suspected meningitis were sent to the Hellenic National Meningitis Reference Laboratory. Ten of 545 (1.83%) patients died. Analysis by receiver operating characteristics (ROC) curve revealed that both suPAR and age were significant for prediction of fatal outcome. Patients with levels of suPAR above the cut-off values and age ≥ 51 years, or patients in which either Neisseria meningitis or Streptococcus pneumoniae were detected were categorized as high risk patients. The combination of the above three predictors (suPAR, age and infectious agent) in a logistic regression model with outcome of infection as the dependent variable yielded an overall odds ratio (OR = 85.7, 95% CI 10.6-690.2) with both sensitivity and specificity being equal to the value of 0.9. In conclusion, suPAR, age and type of infection have an additive effect in predicting mortality among patients suspected of meningitis.

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“…PLAUR is cleaved and becomes soluble, which is released into blood and other body fluids, binds to cell surface, and elicits various responses [19,20]. Soluble PLAUR has been identified as a plasma biomarker of myeloma [21], prostate cancer [22,23], ovarian cancer [24], colorectal cancer [25], small cell lung cancer [26], respiratory cancer [27], cervical cancer [28], and breast cancer [29].…”

Section: Introductionmentioning

confidence: 99%

PLAUR Confers Resistance to Gefitinib Through EGFR/P-AKT/Survivin Signaling Pathway

Zhou

Kwak

Wu³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Tyrosine kinase inhibitor gefitinib significantly improves the survival of patients with non-small-cell lung cancer (NSCLC) by inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase. However, patients eventually develop resistance to gefitinib through uncharacterized mechanisms. It is known that plasminogen activator urokinase receptor (PLAUR) plays an important role in cell proliferation, migration and apoptosis. However, the role of PLAUR, particularly exosomal PLAUR in gefitinib resistance in NSCLC has not been reported. The aim of this study is to determine the relationship between PLAUR and gefitinib resistance. Methods: In this study, a tethered cationic lipoplex nanoparticle (TCLN) biochip containing molecular beacons was used as probes to detect PLAUR mRNA in plasma exosomes from patients with gefitinib-sensitive and -resistant NSCLC. In vitro, Real-time PCR was used to examine the expression of PLAUR mRNA and Western blot was applied to examine the expression of related proteins. The gene knockdown was achieved by Lentivirus based RNA silence technique. The cell counting kit-8 assay and EdU incorporation were used to examine cell proliferation. The flow cytometry was applied to determine cell apoptosis and cell cycle, while the mitochondrial membrane potential was measured by JC-1 dye assay. Signaling pathway affected by PLAUR knockdown was identified by cDNA Microarray. The effect of PLAUR knockdown on tumorigenesis was analyzed in vivo. Results: We found that the exosomal PLAUR mRNA in the plasma of gefitinib-resistant NSCLC patients was significantly increased compared to that of gefitinib-sensitive NSCLC patients. The PLAUR mRNA and soluble PLAUR protein were also significantly increased in gefitinib-resistant human lung adenocarcinoma PC9R cells compared to gefitinib-sensitive PC9 cells. Silencing PLAUR in PC9R cells impaired mitochondrial membrane potential and increased cell apoptosis via EGFR/p-AKT/survivin signaling pathway. Furthermore, EGFR was upregulated in the geftinib-resistant PC9R cells, and knockdown of EGFR significantly increased cell apoptosis. Conclusions: Taken together, our results demonstrated that PLAUR induces geftinib-resistance through EGFR/p-AKT/survivin signaling pathway in gefitinib-resistant human lung adenocarcinoma cells. PLAUR could be a novel therapeutic target for gefitinib-resistant NSCLC patients.

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Prognostic value of intact and cleaved forms of the urokinase plasminogen activator receptor in a retrospective study of 518 colorectal cancer patients

Cited by 49 publications

References 21 publications

Prognosis in adenocarcinomas of lower oesophagus, gastro‐oesophageal junction and cardia evaluated by uPAR‐immunohistochemistry

Prognosis in adenocarcinomas of lower oesophagus, gastro‐oesophageal junction and cardia evaluated by uPAR‐immunohistochemistry

Elevated soluble urokinase receptor values in CSF, age and bacterial meningitis infection are independent and additive risk factors of fatal outcome

PLAUR Confers Resistance to Gefitinib Through EGFR/P-AKT/Survivin Signaling Pathway

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