Production of endothelin-1 and thrombomodulin by human pancreatic cancer cells

Oikawa, Tetsuro; Kushuhara, M; Ishikawa, Shiro; Hitomi, Jiro; Kono, Akira; Iwanaga, Tomohiro; Yamaguchi, Ken

doi:10.1038/bjc.1994.208

Cited by 42 publications

(23 citation statements)

References 25 publications

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“…It is also a high affinity 'thrombin receptor', but its role in tumour biology is not yet completely understood. Our finding of detectable levels of expression in a proportion of pancreatic cancer cell lines confirms a recent report [19] in which 11 out of 12 lines contained detectable expression of TM, often with secretion into the culture medium. Increased levels of plasma TM have been found in patients with pancreatic cancer [20].…”

Section: Discussionsupporting

confidence: 79%

A Characterization of the Coagulant and Fibrinolytic Profile of Human Pancreatic Carcinoma Cells

Kakkar

Chinswangwatanakul

Tebbutt

et al. 1998

Pathophysiol Haemos Thromb

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The activation of coagulation and fibrinolytic pathways is well recognized in patients with malignant disease including those with carcinoma of the pancreas. The elaboration of activators and inhibitors of coagulation and of fibrinolysis has been assessed in 8 human pancreatic adenocarcinoma cell lines in vitro. Tissue factor (TF) was commonly synthesized with wide variations in the amount produced between cell lines, whereas its inhibitor (tissue factor pathway inhibitor, TFPI) showed lower but more consistent levels. Of the activators of fibrinolysis, urokinase was produced by all but one cell line, whereas tissue plasminogen activator expression was much less frequently seen. A correlation between low TF or high TFPI and cell doubling time was demonstrated. These data suggest a complex interaction of tumour-derived enzymes capable of interacting with most haemostatic mechanisms.

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Section: Discussionsupporting

confidence: 79%

A Characterization of the Coagulant and Fibrinolytic Profile of Human Pancreatic Carcinoma Cells

Kakkar

Chinswangwatanakul

Tebbutt

et al. 1998

Pathophysiol Haemos Thromb

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“…Indicated are mean values (±SD) of the total score and the fibrosis score. For comparison, averaged scores of two healthy rats (neither DBTC nor bosentan application) are shown as well receptor axis in pancreatic cancer as well as pancreatic stellate cells [19][20][21][22][23][24]. PSC are the key effector cells in pancreatic fibrosis, a characteristic feature of PC and an important factor with respect to disease progression [2,5,13,14].…”

Section: Discussionmentioning

confidence: 99%

“…Components of the ET-1/ET receptor axis are also frequently expressed in pancreatic cancer cells [23,24]. In a recent study, Bhargava et al showed that LU-302146, a specific antagonist of endothelin receptor type A (ET R A), inhibited the growth of ET R A-positive pancreatic cancer cell lines in vitro and in vivo, and displayed anti-angiogenic effects [24].…”

Section: Introductionmentioning

confidence: 98%

Synergistic Growth Inhibitory Effects of the Dual Endothelin-1 Receptor Antagonist Bosentan on Pancreatic Stellate and Cancer Cells

et al. 2008

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Pancreatic stellate cells (PSC) play a key role in pancreatic fibrosis. Activation of PSC occurs in response to pro-fibrogenic stimuli and is maintained by autocrine loops of mediators, such as endothelin (ET)-1. Here, we have evaluated effects of the dual ET receptor antagonist bosentan in models of pancreatic fibrogenesis and cancer. Cell culture studies revealed that PSC and DSL6A pancreatic cancer cells expressed both ET-1 and ET receptors. Bosentan efficiently inhibited proliferation of both cell types and collagen synthesis in PSC. Expression of the myofibroblastic marker alpha-smooth muscle actin, connective tissue growth factor, and ET-1 itself in PSC was reduced, while expression of matrix metalloproteinase-9 was enhanced. Like PSC, DSL6A cells secrete less ET-1 when cultured with bosentan. In a rat model of pancreatic fibrosis, chronic pancreatitis induced by dibutyltin dichloride, a tendency towards a diminished disease progression was observed in a subgroup of rats with less severe disease. Together, our results indicate that bosentan exerts antifibrotic and antitumor effects in vitro. Its efficiency in vivo warrants further investigation.

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“…Assays VEGF and ET-1 levels were determined by means of ELISA assay (R&D Systems, Inc., Minneapolis, MN, USA) [22,23]. ProET-1 was detected using an assay in the chemiluminescence-coated tube format as described previously (Brahms AG, Henningsdorf Berlin, Germany) [19,24].…”

Section: Patientsmentioning

confidence: 99%

Increase of angiogenic growth factors after hepatic artery embolization in patients with neuroendocrine tumours

et al. 2011

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In the event of diffuse hepatic metastases, hepatic artery embolization (HAE) can be a successful treatment option in patients with well-differentiated neuroendocrine tumours (NET). However, embolization causes hypoxia which stimulates angiogenesis and therefore tumour growth. This study investigates angiogenesis activity following HAE by measuring vascular endothelial growth factor (VEGF), endothelin-1 (ET-1) and C-terminal proendothelin-1 (proET-1) in blood. Twelve patients with well-differentiated NET and liver metastases underwent HAE. VEGF, ET-1 and proET-1 were measured before embolization and the days following treatment during hospitalization. Mean levels during treatment were compared with those at baseline. From 12 patients, 90 blood samples were obtained before and daily for 8 days following HAE. Mean (± SE) VEGF level at baseline was 116 (± 33)ng/l which increased after HAE to 313 (± 46)ng/l at day 6, followed by a gradual decrease. ProET-1 showed a similar pattern, with a mean baseline level of 9.2 (± 2.0)pmol/l and the highest level of 40.8 (± 5.7)pmol/l at day 6. Some fluctuations were observed for ET-1, with maximum levels at day 3 compared to baseline levels. In patients with well-differentiated NET who underwent hepatic arterial embolization, angiogenic growth factors increase temporarily. This implies a need to investigate the effect of anti-angiogenic drugs as an adjuvant therapy to embolization.

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Production of endothelin-1 and thrombomodulin by human pancreatic cancer cells

Cited by 42 publications

References 25 publications

A Characterization of the Coagulant and Fibrinolytic Profile of Human Pancreatic Carcinoma Cells

A Characterization of the Coagulant and Fibrinolytic Profile of Human Pancreatic Carcinoma Cells

Synergistic Growth Inhibitory Effects of the Dual Endothelin-1 Receptor Antagonist Bosentan on Pancreatic Stellate and Cancer Cells

Increase of angiogenic growth factors after hepatic artery embolization in patients with neuroendocrine tumours

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