Up-regulation of urokinase-type plasminogen activator in squamous cell carcinoma of human larynx

Parolini, Silvia; D, Flagiello; Cinquetti, A.; Gozzi, R.; Cristini, Silvia; Cappiello, Johnny; Nicolai, Piero; Rusnati, Marco; Presta, Marco; Tosatti, Maria Pia Molinari

doi:10.1038/bjc.1996.512

Cited by 18 publications

(14 citation statements)

References 35 publications

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“…We observed higher levels of uPA and PAI‐1 in tumor tissues when compared with their normal counterparts. This is in accordance with other studies concerning HNSCC that reported significantly higher uPA and PAI‐1 levels in tumor specimens than in their normal counterparts 25–33. Recently, using expression profiling, Chin et al34 noted that PAI‐1 was listed in the top 5% of genes that differed at a level of statistical significance between mucosa and tumor.…”

Section: Discussionsupporting

confidence: 87%

Prognostic value of plasminogen activator inhibitor‐1 in head and neck squamous cell carcinoma

et al. 2006

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Background. Tumor cell biological factors, such as urokinase plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor-1 (PAI-1), cathepsin D, and c-myc play a role in tumor invasion, metastasis, and proliferation. In this study, the prognostic importance of these factors in patients with primary head and neck squamous cell carcinoma (HNSCC) was evaluated and correlated with clinicopathologic variables.Methods. In 46 paired primary tumors and normal tissues, levels of uPA, PAI-1, cathepsin D, and c-myc amplification were determined. The clinical follow-up was over 10 years. Relationships between cell biological factors and patient and tumor characteristics were studied by the Mann-Whitney test. The Cox proportional hazard model was used for univariate and multivariate analysis.Results. In this study, only a high level of PAI-1 was associated with a significantly shorter disease-free survival (p < .01). PAI-1 levels were higher in tumors with perineural invasion (p < .01). Both PAI-1 and uPA levels were higher in patients who smoked (p < .01 and p ¼ .02). In univariate analysis, smoking (p ¼ .04), excessive alcohol intake (p ¼ .02), perineural invasion (p ¼ .001), and vaso-invasion (p ¼ .009) were associated with a shorter disease-free survival. The only factor related to overall survival was perineural invasion (p ¼ .045). The combination of a high PAI-1 level and perineural invasion appeared to be a significant predictor of a shorter disease-free interval (p ¼ .01).Conclusion. PAI-1 may present a novel prognostic factor for patients with HNSCC. Perineural invasion and PAI-1 level combined seemed to be prognostic for disease-free survival. Keywords: head and neck cancer; uPA; PAI-1; perineural; invasion Head and neck squamous cell carcinoma (HNSCC) represents the sixth most common cancer worldwide. 1 Annually there are approximately 500,000 new cases of HNSCC worldwide, 2500 cases in The Netherlands alone. 2,3 Despite advances in diagnosis and therapy, long-term survival of HNSCC patients has only moderately improved during the past 20 years. This is due to the relatively high local recurrence rate, metastatic spread, and secondary primary cancers. About 10% to 20% of the patients develop regional recurrences, 4,5 25% to 30% distant metastases, 6 and 5% to 36% develop a second primary tumor in the head and neck region. 4 Tumor status and especially cervical lymph node status are regarded as the most important prognostic factors for overall survival. It has been reported that the 5-year overall survival is reduced by approximately 50% in patients with a node Correspondence to: E. M. J. J. Berns

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Section: Discussionsupporting

confidence: 87%

Prognostic value of plasminogen activator inhibitor‐1 in head and neck squamous cell carcinoma

et al. 2006

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“…[10][11][12]25,26 Considering larynx squamous carcinoma, a previous report analyzing uPA expression by in situ hybridization described higher expression in tumor as compared with its normal adjacent tissue. 13 We failed in showing a similar relationship in our series in accordance with a previous report 14 in which small differences in uPA concentrations between tumor and normal larynx tissue were described. n = 10 n = 7 n = 11 n = 5 n = 6…”

Section: Discussionsupporting

confidence: 54%

“…In disagreement with our results, a previous report suggested that the extent of uPA protein activity may be associated to lymph node metastasis. 13 Since the same author suggested that the uPA antigen or activity levels depend, at least in part, on the expression of uPA gene, one explanation for such differences might be a reflection of our study population.…”

Section: Discussionmentioning

confidence: 94%

Transforming growth factor β1, urokinase‐type plasminogen activator and plasminogen activator inhibitor‐1 mRNA expression in head and neck squamous carcinoma and normal adjacent mucosa

Pasini¹,

Brentani²,

Kowalski³

et al. 2001

Head & Neck

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“…PLAU and MMP14 are proteases which promote tumor invasiveness and metastasis through their involvement in the degradation of the extracellular matrix. They have been previously implicated in HNC as well as other tumor types, and their inhibition has been explored for therapeutic purposes (17,(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47). IGFBP7 is a tumor suppressor protein shown to be down-regulated in solid tumors of the liver, lung, breast, prostate, colon, and skin (48 -50).…”

Section: Discussionmentioning

confidence: 99%

Potentially Novel Candidate Biomarkers for Head and Neck Squamous Cell Carcinoma Identified Using an Integrated Cell Line-based Discovery Strategy

Sepiashvili

Hui

Ignatchenko

et al. 2012

Molecular & Cellular Proteomics

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Head and neck squamous cell carcinomas (HNSCC) can arise from the oral cavity, oropharynx, larynx or hypopharynx, and is the sixth leading cancer by incidence worldwide. The 5-year survival rate of HNSCC patients remains static at 40 -60%. Hence, biomarkers which can improve detection of HNSCC or early recurrences should improve clinical outcome. Mass spectrometry-based proteomics methods have emerged as promising approaches for biomarker discovery. As one approach, mass-spectrometric identification of proteins shed or secreted from cancer cells can contribute to the identification of potential biomarkers for HNSCC and our understanding of tumor behavior. In the current study, mass spectrometry-based proteomic profiling was performed on the conditioned media (i.e. secretome) of head and neck cancer (HNC) cell lines (FaDu, UTSCC8 and UTSCC42a) in addition to gene expression microarrays to identify over-expressed transcripts in the HNSCC cells in comparison to a normal control cell line. This integrated data set was systematically mined using publicly available resources (Human Protein Atlas and published proteomic/transcriptomic data) to prioritize putative candidates for validation. Subsequently, quantitative real-time PCR (qRT-PCR), Western blotting, immunohistochemistry (IHC), and ELISAs were performed to verify selected markers. Our integrated analyses identified 90 putative protein biomarkers that were secreted or shed to the extracellular space and over-expressed in HNSCC cell lines, relative to controls. Subsequently, the over-expression of five markers was verified in vitro at the transcriptional and translational levels using qRT-PCR and Western blotting, respectively. IHC-based validation conducted in two independent Head and Neck Squamous Cell Carcinoma (HNSCC)1 is the sixth most common cancer worldwide, with ϳ600,000 new cases diagnosed every year (1). HNSCCs include squamous cell carcinomas (SCCs) of the oral cavity, pharynx (nasopharynx, oropharynx, and hypopharynx), and larynx. Despite improvements in therapeutic approaches, the overall 5-year survival rate of HNSCC patients has not improved over the past three decades (1, 2).Clinical management of HNSCC is faced by several challenges, including early detection of the primary tumor, and site-specific control of the disease (3, 4). Early diagnosis is often hampered by the asymptomatic nature of HNSCC development and the inadequacy of current diagnostic methods to identify HNSCCs with sufficient specificity and sensitivity. As a result, over 60% of HNSCC patients present with advanced stages III or IV, harboring lymph node metastases (3).

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Up-regulation of urokinase-type plasminogen activator in squamous cell carcinoma of human larynx

Cited by 18 publications

References 35 publications

Prognostic value of plasminogen activator inhibitor‐1 in head and neck squamous cell carcinoma

Prognostic value of plasminogen activator inhibitor‐1 in head and neck squamous cell carcinoma

Transforming growth factor β1, urokinase‐type plasminogen activator and plasminogen activator inhibitor‐1 mRNA expression in head and neck squamous carcinoma and normal adjacent mucosa

Potentially Novel Candidate Biomarkers for Head and Neck Squamous Cell Carcinoma Identified Using an Integrated Cell Line-based Discovery Strategy

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