Tie2/Tek expression in breast carcinoma: Correlations of immunohistochemical assays and long-term follow-up in a series of 909 patients

Dalès, Jean-Philippe; Garcia, Stéphane; Bonnier, Pascal; Duffaud, Florence; Meunier-Carpentier, Séverine; Andrac-Meyer, Lucile; Lavaut, Marie‐Noëlle; Allasia, Claude; Charpin, Colette

doi:10.3892/ijo.22.2.391

Cited by 16 publications

(18 citation statements)

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“…To date, TIE2 protein expression has not been studied in MPM but TIE2 involvement has been reported for breast,24 lung25 and liver tumours 26. In STS we found TIE2 highly associated with PDGFRα and PDGFRβ.…”

Section: Discussionmentioning

confidence: 61%

EGFR and PDGFR differentially promote growth in malignant epithelioid mesothelioma of short and long term survivors

Kothmaier

Quehenberger

Halbwedl

et al. 2008

Thorax

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Background: Malignant pleural mesothelioma (MPM) is an asbestos related tumour difficult to detect early and treat effectively. Asbestos causes genetic modifications and cell signalling events that favour the resistance of MPM to apoptosis and chemotherapy. Only a small number of patients, approximately 10%, survive more than 3 years. The aim of our study was to assess possible differences within signalling pathways between short term survivors (survival ,3 years; STS) and long term survivors (survival .3 years; LTS) of MPM. Methods: 37 antibodies detecting proteins engaged in cell signalling pathways, enforcing proliferation, antiapoptosis, angiogenesis and other cellular activities were investigated by tissue microarray (TMA) technology. Results: Epidermal growth factor receptor (EGFR) was expressed stronger in LTS whereas platelet derived growth factor receptor (PDGFR) signalling was more abundant in STS. Expression of TIE2/Tek, a receptor for tyrosine kinases involved in angiogenesis, was differentially regulated via PDGFR and thus is more important in STS. Antiapoptosis was upregulated in STS by signal transducer and activator of transcription 1 (STAT1)-survivin and related molecules, but not in LTS. Our study provides novel insights into the regulatory mechanisms of signalling pathways in MPM, which differentially promote tumour growth in LTS and STS. Conclusion: We have demonstrated that small scale proteomics can be carried out by powerful linkage of TMA, immunohistochemistry and statistical methods to identify proteins which might be relevant targets for therapeutic intervention.Malignant pleural mesothelioma (MPM) is an asbestos related tumour difficult to detect early and treat effectively.

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Section: Discussionmentioning

confidence: 61%

EGFR and PDGFR differentially promote growth in malignant epithelioid mesothelioma of short and long term survivors

Kothmaier

Quehenberger

Halbwedl

et al. 2008

Thorax

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“…Immunohistologic examination of breast cancer identified Tie2 as an independent unfavorable prognostic indicator. However, this study evaluated the localization (tumor surface positive versus tumor surface negative) but not the intensity of Tie2 expression (40). In contrast, Harris et al reported positive correlation between high soluble Tie2 levels and improved survival and positive response for antiangiogenic therapy in renal cancer (41).…”

Section: Discussionmentioning

confidence: 99%

Angiogenic Switch of Angiopietins-Tie2 System and Its Prognostic Value in Bladder Cancer

Szarvas

Jäger

Tötsch³

et al. 2008

Clinical Cancer Research

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Purpose: Vascular endothelial growth factor (VEGF), angiopoietins (Ang-1and Ang-2), and their receptor Tie2 are critically involved in both normal and pathologic angiogenesis. The aim of this study was to explore the role of Ang-1, Ang-2,VEGF, andTie2 in the development and progression of bladder cancer as well as to examine their prognostic value in this tumor type. Experimental Design:Tumor samples of 113 bladder cancer patients, normal bladder epithelium of 5 noncancer patients, and two low-grade (UMUC3 and RT4) and two high-grade (J82 and T24) bladder cancer cell lines were analyzed by quantitative real-time PCR. The expression data were analyzed performing Wilcoxon rank-sum and Kaplan-Meier log-rank tests as well as univariate Cox analyses and Cox proportional hazards regression model. Results: In tissues of noninvasive bladder tumors, Ang-1 expression was significantly lower (P < 0.001), whereasVEGF expression was significantly higher (P = 0.031) than in normal bladder tissue. These findings were also confirmed at the protein level by immunohistochemistry. In contrast, Tie2 and Ang-2 abundance in tumor did not differ significantly from that in normal bladder tissue. Multivariate analysis identified Ang-2 as a strong and independent predictor of tumor recurrence [hazard ratio (HR), 10.18; 95% confidence interval (95% CI), 2.69-38.49; P < 0.001] andTie2 expression as an independent favorable prognostic factor for both metastasis (HR, 0.31; 95% CI, 0.11-0.89; P = 0.029) and disease-specific survival (HR, 0.25; 95% CI, 0.10-0.62; P = 0.003). Conclusions: These data show the strongest change in expression of VEGF and Ang-1 in superficial bladder cancer in comparison with normal bladder epithelium and the invasive tumor stages. The prognostic significance of Ang-2 and Tie2 underlines the essential role of angiopoietins-Tie2 system in progression of bladder cancer.

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“…This surface protein was found to be a marker of tumor microvasculature [184] correlating with the grade of vascularization and is also a prognostic marker for malignancy [185]. Wu et al identified a peptide sequence GA3 binding to the Tie2 receptor with high affinity and specificity in vitro as well as in vivo [186].…”

Section: Tie2mentioning

confidence: 99%

Specific Targets in Tumor Tissue for the Delivery of Therapeutic Genes

Günther¹,

Wagner²,

Ogris

2005

CMCACA

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Gene therapy is part of a growing field in molecular medicine, which will gain importance in the treatment of human diseases. Until now, almost two thirds of all clinical trials performed in gene therapy are directed against Cancer As solid tumors exceeding a certain size rely on blood supply, the administration of particulate gene delivery vectors via the bloodstream is a promising concept. Tumor cells and the tumor vasculature both offer specific molecular targets, which can be utilized for the site directed delivery of therapeutic genes. Passive targeting of macromolecular drugs including gene delivery vectors to tumors can be achieved by the so called enhanced permeability and retention (EPR) effect. The specificity can be markedly enhanced when tumor targeting ligands are used. Viral vectors, which usually do not have a natural tropism for tumor tissue, were generated to carry tumor targeting molecules on their surface. Synthetic gene delivery vectors, based on cationic lipids or cationic polymers were biochemically modified to incorporate ligands specific for tumor cells or tumor vasculature. For systemic application, these delivery systems have to fulfill certain conditions. The delivery vector should not induce any immunogenic and inflammatory responses. Several studies were conducted to reduce the immunogenicity of viral vectors; surface modification of non-viral gene delivery systems reduced their non-specific interaction with blood components. On the genetic level, tumor specific promoters add additional layers of specificity restricting the transgene expression to the tumor tissue. This review will cover the systemic application of particulate gene transfer vectors targeted to tumors and will give an overview of therapeutic concepts for cancer gene therapy.

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Tie2/Tek expression in breast carcinoma: Correlations of immunohistochemical assays and long-term follow-up in a series of 909 patients

Cited by 16 publications

References 0 publications

EGFR and PDGFR differentially promote growth in malignant epithelioid mesothelioma of short and long term survivors

EGFR and PDGFR differentially promote growth in malignant epithelioid mesothelioma of short and long term survivors

Angiogenic Switch of Angiopietins-Tie2 System and Its Prognostic Value in Bladder Cancer

Specific Targets in Tumor Tissue for the Delivery of Therapeutic Genes

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