Tumour-associated urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 in normal and neoplastic tissues of patients with squamous cell cancer of the oral cavity – clinical relevance and prognostic value

Hundsdorfer, B.; Zeilhofer, Hans‐Florian; Böck, K; Dettmar, P.; Schmitt, Manfred; Kolk, Andreas; Pautke, Christoph; Horch, Hans-Henning

doi:10.1016/j.jcms.2004.12.005

Cited by 72 publications

(68 citation statements)

References 16 publications

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“…Several other groups have previously found significant correlations between uPA and PAI-1 antigen levels in tumor tissue (17,30,34,35,41,42,45,46). These findings may not be surprising considering the various interactions of the members of the plasminogen activation system and the synergic effects ascribed to uPA and PAI-1 in tumor growth and metastasis.…”

Section: Discussionmentioning

confidence: 79%

Quantitative RT-PCR assays for the determination of urokinase-type plasminogen activator and plasminogen activator inhibitor type 1 mRNA in primary tumor tissue of breast cancer patients: Comparison to antigen quantification by ELISA

Biermann

Holzscheiter²,

Kotzsch³

et al. 2008

Int J Mol Med

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Abstract. Urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor type 1 (PAI-1) play a key role in tumor-associated processes such as the degradation of extracellular matrix proteins, tissue remodeling, cell adhesion, migration, and invasion. High antigen levels of uPA and PAI-1 in tumor tissue of various solid malignant tumors, including breast cancer, are associated with poor patient prognosis. In the present study, we examined whether analysis of uPA and PAI-1 mRNA expression represents an alternative to the measurement of the respective antigen levels in breast cancer. Highly sensitive quantitative real-time PCR (QPCR) assays, based on the LightCycler technology, were established to quantify uPA and PAI-1 mRNA expression in breast cancer cell lines as well as in tumor tissue of breast cancer patients. mRNA concentrations were normalized to the expression level of the housekeeping gene h-G6PDH. The respective uPA and PAI-1 antigen concentrations were determined by established ELISA formats. QPCR mean interassay variation coefficients were 11% (uPA) and 8% (PAI-1). In breast cancer cell lines, mRNA and antigen values were highly correlated for both uPA and PAI-1 (each: r s =0.95; p<0.001). In contrast, correlations between uPA/PAI-1 mRNA and protein in the breast cancer samples were found to be distinctly weaker or not significant. Thus, quantitative determination of mRNA expression for both factors does not mirror antigen levels in breast cancer tissue, possibly due to posttranscriptional regulation. Except for nodal status being inversely correlated with uPA mRNA levels, no significant interrelations were observed between uPA or PAI-1 mRNA expression and clinicopathological parameters. On the protein level, elevated uPA and PAI-1 values were associated with a negative steroid hormone receptor status. In conclusion, the implementation of mRNA quantification of uPA and PAI-1 in breast tumors is unable to serve as a one-to-one substitution for antigen determination by ELISA.

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Section: Discussionmentioning

confidence: 79%

Quantitative RT-PCR assays for the determination of urokinase-type plasminogen activator and plasminogen activator inhibitor type 1 mRNA in primary tumor tissue of breast cancer patients: Comparison to antigen quantification by ELISA

Biermann

Holzscheiter²,

Kotzsch³

et al. 2008

Int J Mol Med

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“…Plasmin, in turn, represents a broad spectrum of proteases cleaving extracellular matrix proteins such as fibrin, fibronectin, laminin, and proteoglycans, either directly or via activation of other matrixdegrading enzymes or procollagenases like matrix metalloproteinases (11). Thus, this tumour-associated protease facilitates cell-mediated dissolution of the extracellular matrix, which is necessary for tumour dissemination and possibly recurrence (18).…”

Section: Discussionmentioning

confidence: 99%

Urokinase plasminogen activator expression in canine malignant mammary tumours by immunohistochemical study

Golshahi

Tavasoly

Rezaie

et al. 2013

Bulletin of the Veterinary Institute in Pulawy

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Immunohistochemical expression of urokinase plasminogen activator (uPA) was studied in 37 canine malignant mammary tumours to define the relationship between their histopathological type and grade. In 29 (78.4%) cases, expression of uPA by neoplastic cells was more than 10% and in 34 samples (91.9%) uPA expression by stromal cells (fibroblasts) was more than 10%. The uPA was expressed in epithelial and myoepithelial cells of carcinomas and carcinosarcomas and mesenchymal population of carcinosarcoma, chondrosarcoma, and carcinomas arising in benign tumours. The intensity and percentage of expression of uPA by stromal cells was associated with their histological grade (P < 0.05). However, no significant relationship was detected between uPA expression by neoplastic cells (epithelial, myoepithelial, and mesenchymal cell) and histological grade. Increased expression of uPA by tumour stroma was associated with poor prognostic factors. Stromal expression of uPA could be a prognostic indicator for canine mammary tumours.

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“…MMPs have been described as possible biomarkers of invasion and metastasis in oral cancers (30), which might also apply for the cases examined herein. PLAU has been suggested to be implicated in enhanced cell proliferation and migration (41) and as a prognostic marker for relapse-free survival of OSCCs, together with its receptor uPAR (42). SPARC, or osteonectin, is also implicated in ECM breakdown (43) and has been reported to be associated with tumor progression and metastasis (44).…”

Section: Discussionmentioning

confidence: 99%

Gene expression profile of oral squamous cell carcinomas from Sri Lankan betel quid users

Suhr

Dysvik²,

Bruland³

et al. 2007

Oncol Rep

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Abstract. Oral squamous cell carcinoma (OSCC) is one of the major health problems in Sri Lanka and the disease is associated with the habit of Betel Quid (BQ) chewing. Using 35k oligo microarrays, we analyzed the gene expression profile of 15 Sri Lankan patients diagnosed with OSCCs and pair-wised normal controls and correlated the findings with the clinicopathological data. Following the recording of the scanned array images and data analysis, results for selected candidate genes were verified using QRT-PCR. Upon analysis, a total of 263 genes [71 (27%) of unknown functions previously not reported in OSCCs and 192 (73%) of known functions] were found as differentially expressed between tumors and controls. For the genes with known functions, 66 (34%; such as COL4A1, MMP1, MMP3, PLAU, SPARC and KRT19) were previously reported in OSCC and for the remaining 126 (66%; such as CD47, APOL3, RRAGC, BPIL1 and AZGP1) this is the first report in OSCCs. Hierarchical clustering of the differentially expressed 263 genes grouped the samples into several clusters with the larger one being dominated by tumors of stage 3 and 4. Two cases (a verrucous SCC and an advanced SCC), did not cluster with any of the other samples. We found two main biological pathways (cell communication and integrin-mediated cell adhesion) and 5 gene ontology categories (transcription regulator activity, structural molecule activity, intracellular signaling, cytoskeleton and signal transduction) of relevance to the OSCCs examined. Results from the QRT-PCR verified the results from the microarray experiment. This study provides valuable information on gene expression profile of OSCCs of habitual users of BQ from Sri Lanka. Of particular interest were the list of genes of known and unknown functions and the two biological pathways that we suggest as candidate genes in oral cancers associated with BQ chewing in Southeast Asia, in particular Sri Lanka. The suggested candidate genes might be used as molecular biomarkers in the early detection of the alarming problem of OSCCs in Southeast Asia in association with BQ use. These findings provide valuable information that might help in the selection of possible biomarkers that can be used in early detection of the alarming problem of oral cancer in Southeast Asia.

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Tumour-associated urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 in normal and neoplastic tissues of patients with squamous cell cancer of the oral cavity – clinical relevance and prognostic value

Cited by 72 publications

References 16 publications

Quantitative RT-PCR assays for the determination of urokinase-type plasminogen activator and plasminogen activator inhibitor type 1 mRNA in primary tumor tissue of breast cancer patients: Comparison to antigen quantification by ELISA

Quantitative RT-PCR assays for the determination of urokinase-type plasminogen activator and plasminogen activator inhibitor type 1 mRNA in primary tumor tissue of breast cancer patients: Comparison to antigen quantification by ELISA

Urokinase plasminogen activator expression in canine malignant mammary tumours by immunohistochemical study

Gene expression profile of oral squamous cell carcinomas from Sri Lankan betel quid users

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