Regulation of thrombomodulin expression in prostate cancer cells

Menschikowski, Mario; Hagelgans, Albert; Tiebel, Oliver; Vogel, Margot; Eisenhofer, Graeme; Siegert, Gabriele

doi:10.1016/j.canlet.2012.03.001

Cited by 11 publications

(6 citation statements)

References 47 publications

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“…This is in agreement with a previous study of bladder cancer, which demonstrated that decreased TM expression level is a predictor of aggressiveness in advanced bladder cancer [54]. TM expression was also shown to be decreased in human prostate cancer cell lines, DU-145, LNCaP and PC-3 as compared to normal prostate epithelial cells PrEC [55].…”

Section: Discussionsupporting

confidence: 93%

IL-10 correlates with the expression of carboxypeptidase B2 and lymphovascular invasion in inflammatory breast cancer: The potential role of tumor infiltrated macrophages

Mohamed

El-Husseiny

El-Ghonaimy

et al. 2018

Current Problems in Cancer

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Pro-carboxypeptidase B2 (pro-CPB2) or thrombin-activatable ﬁbrinolysis inhibitor (TAFI) is a glycoprotein encoded by the CPB2 gene and deregulated in several cancer types, including breast cancer. Thrombin binding to thrombomodulin (TM), encoded by THBD, is important for TAFI activation. CPB2 gene expression is influenced by genetic polymorphism and cytokines such as interleukin 10 (IL-10). Our previous results showed that tumor infiltrating monocytes/macrophages (CD14/CD16) isolated from inflammatory breast cancer (IBC) patients' secrete high levels of IL-10. The aim of the present study is to test genetic polymorphism and expression of CPB2 in healthy breast tissues and carcinoma tissues of non-IBC and IBC patients. Furthermore, to investigate whether IL-10 modulates the expression of CPB2 and THBD in vivo and in-vitro. We tested CPB2 Thr325Ile polymorphism using restriction fragment length polymorphism, (RFLP) technique in healthy and carcinoma breast tissues. The mRNA expression of CPB2, THBD and IL10 were assessed by RT-qPCR. Infiltration of CD14 cells was assessed by immunohistochemistry. In addition, we investigated the correlation between infiltration of CD14 cells and expression of IL10 and CPB2. Furthermore, we correlated IL10 expression with the expression of both CPB2 and THBD in breast carcinoma tissues. Finally, we validated the role of recombinant IL-10 in regulating the expression of CPB2 and THBD using different breast cancer cell lines. Our results showed that CPB2 genotypes carrying the high-risk allele [Thr/Ile (CT) and Ile/Ile (TT)] were more frequent in both IBC and non-IBC patients compared to control group. CPB2 genotypes did not show any statistical correlation with CPB2 mRNA expression levels or patients' clinical pathological properties. Interestingly, CPB2 and IL10 expression were significantly higher and positively correlated with the incidence of CD14 cells in carcinoma tissues of IBC as compared to non-IBC. On the other hand, THBD expression was significantly lower in IBC carcinoma versus non-IBC tissues. Based on molecular subtypes, CPB2 and IL10 expression were significantly higher in triple negative (TN) as compared to hormonal positive (HP) carcinoma tissues of IBC. Moreover, CPB2 expression was positively correlated with presence of lymphovascular invasion and the expression of IL10 in carcinoma tissues of IBC patients. Furthermore, recombinant human IL-10 stimulated CPB2 expression in SUM-149 (IBC cell line) but not in MDA-MB-231 (non-IBC cell line), while there was no significant effect THBD expression. In conclusion, carcinoma tissues of IBC patients are characterized by higher expression of CPB2 and lower expression of THBD. Moreover, CPB2 positively correlates with IL10 mRNA expression, incidence of CD14 cells and lymphovascular invasion in IBC patients. IL-10 stimulated CPB2 expression in TN-IBC cell line suggests a relevant role of CPB2 in the aggressive phenotype of IBC.

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Section: Discussionsupporting

confidence: 93%

IL-10 correlates with the expression of carboxypeptidase B2 and lymphovascular invasion in inflammatory breast cancer: The potential role of tumor infiltrated macrophages

Mohamed

El-Husseiny

El-Ghonaimy

et al. 2018

Current Problems in Cancer

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“…Aberrant DNA methylation plays a key role in carcinogenesis, leading to the epigenetic silencing of the expression of tumor-suppressor genes. Moreover, the expression of TM was restored after treatment with DNMT inhibitor in certain types of cancer cells [22,41]. We previously reported [23] that DNMT1 could be a significant clinical predictor of bladder cancer.…”

Section: Discussionmentioning

confidence: 99%

Thrombomodulin expression regulates tumorigenesis in bladder cancer

Chang

Lin

et al. 2014

BMC Cancer

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BackgroundThe identification of potential tumor markers will help improve therapeutic planning and patient management. Thrombomodulin (TM) is a sensitive urothelial marker. TM was reported to be one of the endogenous anti-metastatic factors and has diagnostic and prognostic values for the progression of carcinoma. In the present study, we examine the role of TM in bladder cancer.MethodsWe studied the role of TM in tumor behavior and related signaling pathways in vitro using the human bladder cancer cell lines HT1376, HT1197, J82 and T24, and in vivo using animal models. We also selected clinical specimens from 100 patients with bladder cancer for immunohistochemical staining to evaluate the predictive capacity of TM in tumor invasiveness.ResultsThe data revealed that positive immunoreactivity for TM was inversely correlated with clinical stage and DNA methyltransferase 1 immunoreactivity. Decreased TM expression could predict the aggressive tumor growth and advanced clinical stage in bladder cancer. When TM was inhibited, tumor growth rate and invasion ability were augmented in vitro and in vivo. The underlying changes included increased cell proliferation, enhanced epithelial-mesenchymal transition (EMT) and angiogenesis. Moreover, inhibition of NF-κB activation significantly increased TM expression and attenuated tumor aggressiveness in bladder cancer.ConclusionsTM plays an important role in bladder cancer tumor aggressiveness in vitro and in vivo and is a clinically significant predictor that may represent a suitable therapeutic target for bladder cancer.

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“…However, in PrEC and LNCaP cells, levels of TM were not increased as these cell lines exhibit no or only a low methylated TM promoter. Treatment with 5-aza-dC made DU145 prone to ATRA [89]. It was concluded that ATRA could reduce PC's ability to metastasize.…”

Section: All-trans-retinoic Acid Retinol and Vitamin Amentioning

confidence: 99%

Recent Progress in Discovering the Role of Carotenoids and Their Metabolites in Prostatic Physiology and Pathology with a Focus on Prostate Cancer—A Review—Part I: Molecular Mechanisms of Carotenoid Action

et al. 2021

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Among the vast variety of plant-derived phytochemicals, the group of carotenoids has continuously been investigated in order to optimize their potential application in the area of dietary intervention and medicine. One organ which has been especially targeted in many of these studies and clinical trials is the human prostate. Without doubt, carotenoids (and their endogenous derivatives—retinoids and other apo-carotenoids) are involved in intra- and intercellular signaling, cell growth and differentiation of prostate tissue. Due to the accumulation of new data on the role of different carotenoids such as lycopene (LC) and β-carotene (BC) in prostatic physiology and pathology, the present review aims to cover the past ten years of research in this area. Data from experimental studies are presented in the first part of the review, while epidemiological studies are disclosed and discussed in the second part. The objective of this compilation is to emphasize the present state of knowledge regarding the most potent molecular targets of carotenoids and their main metabolites, as well as to propose promising carotenoid agents for the prevention and treatment of prostatic diseases.

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Regulation of thrombomodulin expression in prostate cancer cells

Cited by 11 publications

References 47 publications

IL-10 correlates with the expression of carboxypeptidase B2 and lymphovascular invasion in inflammatory breast cancer: The potential role of tumor infiltrated macrophages

IL-10 correlates with the expression of carboxypeptidase B2 and lymphovascular invasion in inflammatory breast cancer: The potential role of tumor infiltrated macrophages

Thrombomodulin expression regulates tumorigenesis in bladder cancer

Recent Progress in Discovering the Role of Carotenoids and Their Metabolites in Prostatic Physiology and Pathology with a Focus on Prostate Cancer—A Review—Part I: Molecular Mechanisms of Carotenoid Action

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