Role of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) for prognosis in endometrial cancer

Steiner, Eric; Pollow, K.; Hasenclever, Dirk; Schormann, Wiebke; Hermes, Matthias; Schmidt, M; Puhl, Alexander; Brulport, Marc; Bauer, Alexander; Petry, Ilka; Koelbl, Heinz; Hengstler, Jan G.

doi:10.1016/j.ygyno.2007.11.025

Cited by 39 publications

(24 citation statements)

References 29 publications

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“…From a biological point of view, analysis of protein function would be ideal. However, relatively large amounts of fresh frozen tissue are required for activity assays as well as protein quantification by quantitative immunoblots (34)(35)(36) which are often not available. Therefore, immunostaining is frequently employed, because paraffin material is available Fig.…”

Section: Discussionmentioning

confidence: 99%

ERBB2 and TOP2A in Breast Cancer: A Comprehensive Analysis of Gene Amplification, RNA Levels, and Protein Expression and Their Influence on Prognosis and Prediction

Brase

Schmidt

Fischbach

et al. 2010

Clinical Cancer Research

112

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Purpose: The prognostic and predictive relevance of epidermal growth factor receptor 2 (ERBB2) and topoisomerase II α (TOP2A) have long been a matter of debate. However, the correlation of DNA amplification, RNA levels, and protein expression and their prognostic role and association with anthracycline responses in node-negative breast cancer have not yet been evaluated.Experimental Design: We first analyzed TOP2A and ERBB2 at the levels of gene amplification, and RNA and protein expression, and studied their correlations. Additionally, TOP2A and ERBB2 were analyzed in 782 node-negative breast carcinomas in patients who did not receive systemic therapy and in 80 patients treated with epirubicin and cyclophosphamide (EC) prior to surgery.Results: TOP2A gene amplification did not correlate with protein expression (P = 0.283) and showed an association with gene expression with only borderline significance (P = 0.047). By contrast, TOP2A RNA levels correlated with protein expression (P < 0.001). TOP2A gene expression was significantly associated with the metastasis-free interval (MFI; P < 0.001) and was associated with complete remission in patients treated with EC (P = 0.002). In contrast to TOP2A, ERBB2 gene amplification correlated with RNA level (P < 0.001) and protein expression (P < 0.001). ERBB2 gene expression was associated with the MFI only in estrogen receptor-positive carcinomas, whereas ERBB2 protein expression (P = 0.032) was associated with MFI in the entire cohort.Conclusions: Overall, our study indicates that the TOP2A RNA level is a good prognostic marker and is also associated with a favorable response to anthracyclin-based therapy. By contrast, ESR1 was associated with poorer responses to anthracyclin-based therapy, whereas the association with ERBB2 RNA was not significant. Clin Cancer Res; 16(8); 2391-401. ©2010 AACR.

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Section: Discussionmentioning

confidence: 99%

ERBB2 and TOP2A in Breast Cancer: A Comprehensive Analysis of Gene Amplification, RNA Levels, and Protein Expression and Their Influence on Prognosis and Prediction

Brase

Schmidt

Fischbach

et al. 2010

Clinical Cancer Research

112

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“…Overexpression of PAI-1 has been found in many obesity-related types of cancer and is associated with the progression of breast, endometrial, colorectal, thyroid, renal, and prostate cancer (97)(98)(99)(100)(101)(102). In addition to autocrine production by tumor cells, systemic levels of PAI-1 (e.g., produced by immune cells or adipocytes in obesity) appear to be essential for its tumor-promoting effects, though level dependent (103).…”

Section: Adipokinesmentioning

confidence: 99%

Obesity and Cancer: The Role of Dysfunctional Adipose Tissue

Kruijsdijk

Wall

Visseren

2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

629

532

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Overweight and obesity are health problems of epidemic proportions, increasing the risk not only of cardiovascular disease and type 2 diabetes mellitus but also of various types of cancer. Obesity is strongly associated with changes in the physiological function of adipose tissue, leading to insulin resistance, chronic inflammation, and altered secretion of adipokines. Several of these factors, such as insulin resistance, increased levels of leptin, plasminogen activator inhibitor-1, and endogenous sex steroids, decreased levels of adiponectin, and chronic inflammation, are involved in carcinogenesis and cancer progression. This article reviews these mechanisms, focusing on adipose tissue dysfunction as a unifying causal factor. Although understanding of the link between obesity and cancer might provide therapeutic targets, preventing overweight and obesity still remains number one priority. (Cancer Epidemiol

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“…The uPA is localized predominantly in CAFs at the invasive front of tumors (Pyke et al, 1991), activating plasmin to plasminogen and further enabling the activation of various proteases (Andreasen et al, 2000). Elevated levels of uPA and PAI-1 are associated with an aggressive course (Steiner et al, 2008; Jelisavac-Cosic et al, 2011). In 2007, uPA and PAI-1, as the first-level-of evidence-1 cancer biomarkers, were recommended by the American Society of Clinical Oncology and other national guidelines to assess the risk of patients with breast cancer experiencing disease recurrence and to predict response to systemic adjuvant chemotherapy (Schmitt et al, 2010).…”

Section: Functional Roles Of Cafs In Cancer Progressionmentioning

confidence: 99%

Tumor stroma as targets for cancer therapy

Zhang

Liu

2013

Pharmacology & Therapeutics

158

121

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Cancer is not only composed malignant epithelial component but also stromal components such as fibroblasts, endothelial cells, and inflammatory cells, by which an appropriate tumor microenvironment (TME) is formed to promote tumorigenesis, progression, and metastasis. As the most abundant component in the TME, cancer-associated fibroblasts (CAFs) are involved in multifaceted mechanistic details including remodeling the extracellular matrix, suppressing immune responses, and secreting growth factors and cytokines that mediate signaling pathways to extensively affect tumor cell growth and invasiveness, differentiation, angiogenesis, and chronic inflammatory milieu. Today, more and more therapeutic strategies are purposefully designed to target the TME as well as tumor cells. This review will focus on the role of CAFs in tumor development and the novel strategies to target this component to inhibit the tumor growth.

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Role of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) for prognosis in endometrial cancer

Cited by 39 publications

References 29 publications

ERBB2 and TOP2A in Breast Cancer: A Comprehensive Analysis of Gene Amplification, RNA Levels, and Protein Expression and Their Influence on Prognosis and Prediction

ERBB2 and TOP2A in Breast Cancer: A Comprehensive Analysis of Gene Amplification, RNA Levels, and Protein Expression and Their Influence on Prognosis and Prediction

Obesity and Cancer: The Role of Dysfunctional Adipose Tissue

Tumor stroma as targets for cancer therapy

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