Plasminogen- and colony-stimulating factor-1-associated markers in bladder carcinoma: diagnostic value of urokinase plasminogen activator receptor and plasminogen activator inhibitor type-2 using immunocytochemical analysis

Champelovier, Pierre; Boucard, Nathalie; Levacher, Géraldine; Simon, Annick; Seigneurin, Daniel; Perreten, Vincent

doi:10.1007/s00240-002-0270-5

Cited by 35 publications

(23 citation statements)

References 26 publications

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“…In leukemic patients, over-expression of the UPA-R is associated with increased consumption of plasma inhibitors, leading to increased bleeding complications [1]. Some authors could correlate increased expression of the UPA-R on tumor cells (e.g., bladder carcinoma, breast cancer, dermatological tumors) with a worse prognosis for the patients [19][20][21][22]. We observed that a high expression rate of UPA-R on AML cells was significantly correlated with a lower remission rate (P ¼ 0.03) and also with shorter progress-free survival times, thus confirming data reported by other authors with respect to solid tumors.…”

Section: Upa-r Mediates Adhesion and Migration Of Tumor Cells And Hasmentioning

confidence: 99%

High expression of urokinase plasminogen activator receptor (UPA-R) in acute myeloid leukemia (AML) is associated with worse prognosis

Graf¹,

Reif²,

Hecht³

et al. 2005

Am. J. Hematol.

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Urokinase-type plasminogen activator receptor (UPA-R; CD87) is a membrane protein responsible for plasmin expression on cells facilitating cellular extravasations and tissue invasions. We studied the expression of the UPA-R on bone marrow (BM) cells of 93 patients with acute myeloid leukemia at first diagnosis and 8 healthy probands as controls by FACS analysis using phycoerythrin (PE)-conjugated antibodies. A case was defined as UPA-R-positive (UPA-R + ) if >20% of the gated cells expressed UPA-R. Whereas none of the 8 healthy BM samples was positive for the UPA-R, 32 (34%) of the 93 AML samples were UPA-R + . Expression of UPA-R was heterogeneous in different FAB types, however, with the highest expression rates in monocytic subtypes (FAB M4/M5): 18%/19%/30% of UPA-R + cases were found in M1/M2 or M3, and 58%/80% of cases with M4 or M5 were UPA-R + .Proportions of UPA-R + cells varied between 1% and 98% of the mononuclear cell fractions, with the highest proportions in M4/M5 subtypes (on average 27%/40% UPA-R + cells) and the lowest expression in AML M2 (11% UPA-R + cells). The density of expressed UPA-R, estimated as mean channel fluorescence activity, was highest in cases with AML M1 (mFI: 124) followed by M4 and M5 (mFI: 78/77) and lowest in AML M2 (mFI: 43). In sAML, higher proportions of UPA-R + cases (8 of 18; 44%) compared to pAML (24 of 75; 32%) were found as well as higher proportions of UPA-R + cells (27% vs. 19%). Separating our patients' cohort in cytogenetic risk groups, we could not detect significant differences in the UPA-R expression profiles. For evaluations of the clinical course of AML, only patients treated by the AML-CG protocol (n = 65) were included. In the group of patients who did not respond to AML-CG therapy, significantly higher proportions of UPA-R + cells (31% vs. 14%, P = 0.0015, t-test) were found. By evaluating a cut-off value for the percentage of positive cells that allows the most significant separation and differentiation between cases with shorter or longer relapse-free survival times, we could show that patients with >26.5% UPA-Rpositive cells were characterized by a significantly higher risk for relapse compared to cases with <26.5% positive cells (P = 0.05). In summary, our data show a high expression of the UPA-R in AML, especially in (myelo)monocytoid subtypes. Cases with higher proportions of UPA-R + cells were characterized by a significant lower remission rate after AML-CG therapy and a higher risk for relapse. Although prospective trials are still lacking, UPA-R is a prognostically relevant factor independent from the karyotype. UPA-R positivity may identify subtypes of AML associated with a more aggressive clinical course. Thus due to lower remission probabilities in UPA-R + cases, a more intensive induction therapy regimen could be considered. Am.

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Section: Upa-r Mediates Adhesion and Migration Of Tumor Cells And Hasmentioning

confidence: 99%

High expression of urokinase plasminogen activator receptor (UPA-R) in acute myeloid leukemia (AML) is associated with worse prognosis

Graf¹,

Reif²,

Hecht³

et al. 2005

Am. J. Hematol.

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“…SERPINB5 was also found specifically downregulated by the TA1 truncation. SERPINB5 has been identified as a biomarker for several cancer types, including bladder (Cohen et al, 1989;Foucre et al, 1991;Hudson and McReynolds, 1997;Champelovier et al, 2002). SERPINB5 is synthesized in two forms originating from single mRNA species, an intracellular nonglycosylated form (46 543 kDa) and an extracellular glycosylated form (60 kDa) (for a review, see (Bachmann, 1995)).…”

Section: Discussionmentioning

confidence: 99%

DBC1 re-expression alters the expression of multiple components of the plasminogen pathway

et al. 2005

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Deleted in bladder cancer 1 (DBC1) is a candidate gene for the bladder tumour suppressor locus at 9q33.1. The function of the gene is currently unknown but a crossspecies sequence comparison suggests an important role, as it is highly evolutionarily conserved. Here, we transfected a nonexpressing human bladder cancer cell line with a set of human DBC1 cDNA constructs. The effect on global expression patterns was assessed using cDNA microarrays. The cell clone with the lowest level of DBC1 expression showed induced expression of 26 genes including plasminogen activator inhibitor 2 (SERPINB5; 4.6-fold), heparin-binding EGF-like growth factor precursor (DTR; 4.2-fold), small proline-rich protein 2B (SPRR2B; 3.6-fold), metallothionein 1 isoforms (MT1B/ MT1A/MT-1F; from 2.9-to 3.2-fold), tissue-type plasminogen activator precursor (PLAT; 2.8-fold) and urokinase-type plasminogen activator precursor (PLAU; 2.7-fold). In clustering analysis, both PLAT and PLAU clustered with the functionally related urokinase plasminogen activator surface receptor (PLAUR; 1.9-fold). Furthermore, 14 human bladder tumours were analysed by real-time quantitative PCR using gene-specific primers for selected (n ¼ 20) genes. The expression levels of SERPINB5, PLAU, PLAUR and MT1 correlated with the DBC1 levels, suggesting previously unknown involvement of DBC1 in the urokinase-plasminogen pathway.

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“…Its up-regulation correlated with disease progression and poor long-term survival (Cheng et al, 2002(Cheng et al, , 2005Joseph et al, 1995;Miyata et al, 2009). A significant association between the expression of uPA and uPAR was observed in BCa tissues; both factors were higher in muscle-invasive than in non-muscle invasive BCa and correlated with a worse outcome (Champelovier et al, 2002;Hasui et al, 1994;Seddighzadeh et al, 2002). Elevated levels of uPA and uPAR were also detected in urine and plasma samples from BCa patients compared to controls without BCa (Casella et al, 2002;Shariat et al, 2003).…”

Section: Tumor Angiogenesis and Metastasismentioning

confidence: 94%

Bladder Cancer Biology

Fuessel¹,

Kunze²,

Wirth³

2012

Bladder Cancer - From Basic Science to Robotic Surgery

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At present, bladder cancer (BCa) is worldwide the 9 th most common tumor; in men it represents the 7 th and in women 17 th most common malignancy (Ploeg et al., 2009). In the European Union approximately 104,400 newly diagnosed BCa and 36,500 BCa-related deaths were estimated for the year 2006 (Ferlay et al., 2007). In the United States, approximately 70,530 new cases and 14,680 BCa-related deaths were expected for 2010 (Jemal et al., 2010). Men are three to four times more frequently affected than women (Ferlay et al., 2007; Jemal et al., 2010). Detection of BCa is hampered due to lately emerging symptoms, such as hematuria, and the lack of specific tumor markers. Treatment options, particularly for the advanced disease, appear currently insufficient, leading together with the BCa-inherent high recurrence and progression rates to the relatively high BCa-related mortality (Ferlay et al., 2007). For the development of more specific and efficient diagnostic tools and therapeutic approaches a profound understanding of the onset and course of this disease is indispensable. Molecular alterations that presumably lead to malignant transformation of the bladder urothelium belong to specified pathways involved in regulation of cellular homeostasis. As consequence of genetic and epigenetic alterations as well as of changes in subsequent regulatory mechanisms several major cellular processes are influenced in a manner that results in tumor development and progression. Regulation of the cell cycle, cell death and cell growth belong to these processes as well as the control of signal transduction and gene regulation. Particularly important for tumor cell spread and metastasis are changes in the regulation of interactions with stromal cells and extracellular components, of tumor cell migration and invasion and of angiogenesis (Mitra & Cote, 2009). Interestingly, numerous associations between risk factors for the development of BCa and the affected cellular processes were identified (Mitra & Cote, 2009). For tobacco smoking or the occupational exposure to aromatic amines, polycyclic aromatic hydrocarbons and aniline dyes − the major environmental risk factors that contribute to BCa genesis − strong associations with alterations in cell cycle regulation have been reported (

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Plasminogen- and colony-stimulating factor-1-associated markers in bladder carcinoma: diagnostic value of urokinase plasminogen activator receptor and plasminogen activator inhibitor type-2 using immunocytochemical analysis

Cited by 35 publications

References 26 publications

High expression of urokinase plasminogen activator receptor (UPA-R) in acute myeloid leukemia (AML) is associated with worse prognosis

High expression of urokinase plasminogen activator receptor (UPA-R) in acute myeloid leukemia (AML) is associated with worse prognosis

DBC1 re-expression alters the expression of multiple components of the plasminogen pathway

Bladder Cancer Biology

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