The Endothelin Axis Stimulates the Expression of Pro-Inflammatory Cytokines and Pro-Migratory Molecules in Breast Cancer

Jewell, Ashley N; Swamydas, Muthulekha; Castillo, Claudia I; Wyan, Heather; Allen, Lauren; McDermott, Kerri A; Eddy, Jill; Dréau, Didier

doi:10.3109/07357907.2010.496757

Cited by 16 publications

(15 citation statements)

References 55 publications

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“…Furthermore, IL‐17 suppressed apoptosis of several human breast carcinoma cell lines, such as 4T1, MDA MB231 cells . On the contrary, mice implanted with the carcinoma 4T1 cells and then treated with the endothelin‐1 receptor dual antagonist showed decreased levels of TNF‐α and IL‐17 and reduced tumor growth . Similarly, treatment of mice with anti‐TGF‐β antibodies reduced IL‐17 expression both in the tumor and the locoregional lymph nodes .…”

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confidence: 99%

To the Editor IL‐17, an important prognostic factor and potential therapeutic target for breast cancer?

Geng

Zhao

2013

Eur J Immunol

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We read with great interest an article published in the European Journal of Immunology [1], showing that the Th17-related molecules IL-17 and Retinoid-related orphan receptor (ROR) C were elevated in tumor-infiltrating CD4 + and CD8+ T lymphocytes in breast cancer patients. The authors went on to show that angiogenic factors CXCL8, MMP-2, MMP-9, and vascular endothelial growth factor detected within the tumor were possibly induced by IL-17 and indicative of poor disease prognosis [1]. Finally, Th17 cells were also shown to be simultaneously upregulated in breast cancer patients, positively correlated with IL-17, and associated with tumor aggressiveness [1]. These findings suggest that a high level of IL-17 in breast cancer is a poor prognostic factor, and IL-17 may be a potential therapeutic target for breast cancer. Breast cancer occurs in approximately 99.4 of every 100 000 women in North America and is the most frequent malignancy in women. The disease is the second

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confidence: 99%

To the Editor IL‐17, an important prognostic factor and potential therapeutic target for breast cancer?

Geng

Zhao

2013

Eur J Immunol

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“…In line with our results, bosentan inhibited TNF-α and IL-1β production in a mouse model of collagen-induced arthritis in mice (Donate et al 2012), which was correlated with a reduction in the clinical signs of inflammation, including hyperalgesia, leukocyte recruitment, and edema. Bosentan also inhibited TNF-α production during breast cancer bone infiltration (Jewell et al 2010), in endotoxin-induced uveitis (Keles et al 2014), and in paracetamol-induced acute liver toxicity (Yayla et al 2014) in mice.…”

Section: Discussionmentioning

confidence: 98%

“…Pre-clinical studies have suggested the potential of using bosentan to treat a wide range of inflammatory diseases, including arthritis (Donate et al 2012), cancer (Jewell et al 2010), uveitis (Keles et al 2014), and depression (Pinho-Ribeiro et al 2014). Thus, bosentan has been a crucial tool in the investigation of ET-1 roles in disease and perspective of targeting ET-1 to treat diseases.…”

Section: Introductionmentioning

confidence: 98%

Bosentan, a mixed endothelin receptor antagonist, inhibits superoxide anion-induced pain and inflammation in mice

Serafim

Navarro

Zarpelon

et al. 2015

Naunyn-Schmiedeberg's Arch Pharmacol

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Bosentan is a mixed endothelin receptor antagonist widely used to treat patients with pulmonary arterial hypertension, and the emerging literature suggests bosentan as a potent anti-inflammatory drug. Superoxide anion is produced in large amounts during inflammation, stimulates cytokine production, and thus contributes to inflammation and pain. However, it remains to be determined whether endothelin contributes to the inflammatory response triggered by the superoxide anion. The present study investigated the effects of bosentan in a mouse model of inflammation and pain induced by potassium superoxide, a superoxide anion donor. Male Swiss mice were treated with bosentan (10-100 mg/kg) by oral gavage, 1 h before potassium superoxide injection, and the inflammatory response was evaluated locally and at spinal cord (L4-L6) levels. Bosentan (100 mg/kg) inhibited superoxide anion-induced mechanical and thermal hyperalgesia, overt pain-like behavior (abdominal writhings, paw flinching, and licking), paw edema, myeloperoxidase activity (neutrophil marker) in the paw skin, and leukocyte recruitment in the peritoneal cavity. Bosentan also inhibited superoxide anion-induced interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) production, while it enhanced IL-10 production in the paw skin and spinal cord. Bosentan inhibited the reduction of antioxidant capacity (reduced glutathione, ferric reducing antioxidant power, and ABTS radical scavenging ability) induced by the superoxide anion. Finally, we demonstrated that intraplantar injection of potassium superoxide induces the mRNA expression of prepro-endothelin-1 in the paw skin and spinal cord. In conclusion, our results demonstrated that superoxide anion-induced inflammation, pain, cytokine production, and oxidative stress depend on endothelin; therefore, these responses are amenable to bosentan treatment.

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“…Finally, only one study evaluated IL-1α expression using an in vitro model where breast cancer cells were treated with an endothelin-1 (ET-1) receptor dual antagonist, showing a local increase in breast cancer cell secretions of IL-1α [47].…”

Section: Il-1mentioning

confidence: 99%

What Is the Role of Interleukins in Breast Cancer Bone Metastases? A Systematic Review of Preclinical and Clinical Evidence

Salamanna

Borsari

Contartese

et al. 2019

Cancers

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Breast cancer cells produce stimulators of bone resorption known as interleukins (ILs). However, data on the functional roles of ILs in the homing of metastatic breast cancer to bone are still fragmented. A systematic search was carried out in three databases (PubMed, Scopus, Web of Science Core Collection) to identify preclinical reports, and in three clinical registers (ClinicalTrials.gov, World Health Organization (WHO) International Clinical Trials Registry Platform, European Union (EU) Clinical Trials Register) to identify clinical trials, from 2008 to 2019. Sixty-seven preclinical studies and 11 clinical trials were recognized as eligible. Although preclinical studies identified specific key ILs which promote breast cancer bone metastases, which have pro-metastatic effects (e.g., IL-6, IL-8, IL-1β, IL-11), and whose inhibition also shows potential preclinical therapeutic effects, the clinical trials focused principally on ILs (IL-2 and IL-12), which have an anti-metastatic effect and a potential to generate a localized and systemic antitumor response. However, these clinical trials are yet to post any results or conclusions. This inconsistency indicates that further studies are necessary to further develop the understanding of cellular and molecular relations, as well as signaling pathways, both up-and downstream of ILs, which could represent a novel strategy to treat tumors that are resistant to standard care therapies for patients affected by breast cancer bone disease.An initial literature search found 905 references, of which 151 articles were recognized using the PubMed database, 481 articles were recognized using Scopus, and 273 articles were found in the Web of Science Core Collection. Subsequently, the resulting references were submitted to a public reference manager (Mendeley 1.17.11) to eliminate duplicate articles, obtaining 666 articles. From the 666 articles obtained, after exclusion, 116 full-text articles were evaluated, of which 67 met the inclusion criteria. The 560 studies excluded from this review were excluded because they were meeting reports, reviews, book chapters, and case reports, and/or because they reported IL roles in primary breast tumor, as well as in lung, liver, and pulmonary metastasis, leukemia, osteosarcoma, ovarian tumor, melanoma, prostate cancer, autoimmune arthritis related to breast cancer, and other pathological conditions; however, they did not reveal the favorable development of bone metastases from breast cancer. In addition, we excluded studies where IL profiling was derived from breast cancer metastatic patients that were not grouped/analyzed based on the site of metastasis, and where breast cancer bone metastases were evaluated, but no IL roles/functions were examined. Finally, we also eliminated studies where responses to specific therapy (not IL-based) for breast cancer bone metastasis were analyzed, studies that evaluated the contributions of the sensory signaling pathways to neuropathic pain induced by breast cancer bone metastases, and studies on chronic s...

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The Endothelin Axis Stimulates the Expression of Pro-Inflammatory Cytokines and Pro-Migratory Molecules in Breast Cancer

Cited by 16 publications

References 55 publications

To the Editor IL‐17, an important prognostic factor and potential therapeutic target for breast cancer?

To the Editor IL‐17, an important prognostic factor and potential therapeutic target for breast cancer?

Bosentan, a mixed endothelin receptor antagonist, inhibits superoxide anion-induced pain and inflammation in mice

What Is the Role of Interleukins in Breast Cancer Bone Metastases? A Systematic Review of Preclinical and Clinical Evidence

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