Endothelin-1 induces expression of functional CD40 on human vascular smooth muscle cells

Browatzki, Michael; Pfeiffer, Caroline A; Kranzhöfer, Roger

doi:10.1016/s0735-1097(03)82208-8

Cited by 4 publications

(4 citation statements)

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“…Importantly, endothelins also modulate trafficking, differentiation, and activation of tumor-associated immune cells (17)(18)(19)(20)(21)(22)(23)(24), possibly contributing to immune evasion and resistance to immunotherapy (25,26). ET-1 can induce expression of IL-6, MCP-1, and COX-2, key orchestrators of inflammation-mediated cancer cell invasiveness and metastasis via AP-1 and NF-κB (27,28), as well as MMP activity (9,22).…”

Section: Introductionmentioning

confidence: 99%

Tumor endothelin-1 enhances metastatic colonization of the lung in mouse xenograft models of bladder cancer

Said¹,

Smith²,

Sänchez‐Carbayo³

et al. 2011

J. Clin. Invest.

118

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Many patients with advanced bladder cancer develop lethal metastases to the lung. The vasoconstricting protein endothelin-1 (ET-1) has been implicated in this process, although the mechanism(s) by which it promotes metastasis remains unclear. Here, we have evaluated whether tumor ET-1 expression can serve as a biomarker for lung metastasis and whether it is required for metastatic disease. Evaluation of ET-1 mRNA and protein expression in four patient cohorts revealed that levels of ET-1 are higher in patients with muscle-invasive bladder cancers, which are associated with higher incidence of metastasis, and that high ET-1 levels are associated with decreased disease-specific survival. Consistent with its proinflammatory activity, we found that tumorderived ET-1 acts through endothelin-1 receptor A (ET A R) to enhance migration and invasion of both tumor cells and macrophages and induces expression of inflammatory cytokines and proteases. Using human and mouse cancer cells depleted of ET-1 and pharmacologic blockade of ET receptors in lung metastasis models, we found that tumor ET-1 expression and ET A R activity are necessary for metastatic lung colonization and that this process is preceded by and dependent on macrophage infiltration of the lung. In contrast, tumor ET-1 expression and ET A R activity appeared less important in established primary or metastatic tumor growth. These findings strongly suggest that ET A R inhibitors might be more effective as adjuvant therapeutic agents than as initial treatment for advanced primary or metastatic disease.

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Section: Introductionmentioning

confidence: 99%

Tumor endothelin-1 enhances metastatic colonization of the lung in mouse xenograft models of bladder cancer

Said¹,

Smith²,

Sänchez‐Carbayo³

et al. 2011

J. Clin. Invest.

118

View full text Add to dashboard Cite

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“…In addition to MMPs, CD40L was shown to stimulate SMCs to secrete cytokines such as MCP-1, IL-1␤, IL-6, and IL-8 (Lutgens and Daemen 2002;Mukundan et al 2004), contributing further to lesion progression and subsequent instability and rupture. It is worth noting at this point that an increased CD40 expression as well as activity has been reported in SMCs treated with the proatherogenic factors, Ang II and ET-1, via reactive oxygen specie (ROS) and NF-B pathways, respectively, emphasizing as such the important role of CD40L/CD40 dyad in atherosclerosis, as well as the synergy between various vasoactive factors and molecules in disease development (Browatzki et al 2007;Souza et al 2009). The atherogenic function of CD40L/CD40 dyad could even extend to the myofibroblast population in the atherosclerotic lesion.…”

Section: Cd40l Axis In Atherosclerosismentioning

confidence: 99%

CD40 Ligand: A neo-inflammatory molecule in vascular diseases

2012

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“…For example, ET-1 promotes autocrine/paracrine interactions between fibroblasts and cancer cells in prostate and HNSCC cells ( Dawson et al, 2004 ) and modulates trafficking, differentiation, and activation of tumor-associated immune cells, possibly contributing to immune evasion and resistance to immunotherapy ( Kandalaft et al, 2009 ; Grimshaw et al, 2002 ; Buckanovich et al, 2008 ; Said et al, 2011 ). ET-1 can induce expression of IL-6, CCL-2, as well as MMP and COX-2 activity, key orchestrators of inflammation-mediated cancer cell invasiveness and metastasis via AP-1 and NF-κB ( Rosano et al, 2007a , 2001 , 2007b ; Sutcliffe et al, 2009 ; Grimshaw et al, 2002 , 2004 ; Said et al, 2011 ; Browatzki et al, 2007 ; Spinella et al, 2007 ). Recently, we reported that tumor ET-1 triggers inflammation in the lung soon after the cancer cells lodged at this site and thus sets up a vicious cycle wherein inflammatory cells would enhance and facilitate the process of metastatic colonization ( Said et al, 2011 ) ( Fig.…”

Section: Introductionmentioning

confidence: 99%

Permissive role of endothelin receptors in tumor metastasis

Said

Theodorescu

2012

Life Sciences

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Metastasis remains the major driver of mortality in patients with cancer. The multistep metastatic process requires the concerted actions of several genes and involves tumor cell invasion, epithelial mesenchymal transition (EMT), shedding from primary tumor, intravasation, arrest, extravasation and colonization at a preferential site. Understanding this complex process would provide the basis for the development of molecularly targeted therapeutics aimed at the tumor cell or its interaction with the host microenvironment. The neuropeptide hormones endothelins (specially, ET-1) have been correlated with invasiveness and metastasis of several cancers and high ET-1 levels are associated with decreased disease-specific survival. The mechanism(s) by which ET-1 promotes metastasis are being gradually unraveled. Through preferential binding to cognate receptors (ET(A)R or ET(B)R), ET-1 triggers autocrine and paracrine signaling cascades in tumor, immune and stromal cells, at both primary and distant sites, supporting cancer progression and metastasis. In this review, we will summarize the role of the ET axis in metastasis of different cancers and potential targeting of ET receptors in the therapeutic setting.

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Endothelin-1 induces expression of functional CD40 on human vascular smooth muscle cells

Cited by 4 publications

References 0 publications

Tumor endothelin-1 enhances metastatic colonization of the lung in mouse xenograft models of bladder cancer

Tumor endothelin-1 enhances metastatic colonization of the lung in mouse xenograft models of bladder cancer

CD40 Ligand: A neo-inflammatory molecule in vascular diseases

Permissive role of endothelin receptors in tumor metastasis

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