Endothelin-1 promotes vascular endothelial growth factor-dependent angiogenesis in human chondrosarcoma cells

Wu, Min; Huang, Chun‐Yin; Lin, James A.; Wang, S. W.; Peng, Chieh Yu; Cheng, Hsu-Chen; Tang, Chih‐Hsin

doi:10.1038/onc.2013.109

Cited by 95 publications

(76 citation statements)

References 37 publications

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“…In the tumor microenvironment, blood and lymphatic EC increase angiogenesis and lymphangiogenesis in response to ET-1/ ET B R activation. ET-1 induces various stages of neovascularization, also promoting induction of VEGF and displaying a potent additive effect with VEGF family members, in the angiogenic and lymphangiogenic processes (24,32,34).…”

Section: Role Of Et-1 In the Interactions Of Tumor Cells With The Micmentioning

confidence: 99%

Endothelin therapeutics in cancer: Where are we?

Rosanò¹,

Bagnato²

2016

American Journal of Physiology-Regulatory, Integrative and Comp

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In human cancers, the autocrine and paracrine loop mediated by the aberrantly activation of endothelin-1 (ET-1) receptor (ET-1R) elicits pleiotropic effects, preferentially mediated by the scaffold protein ␤-arrestin 1 (␤-arr1), on tumor cells and on the host microenvironment, providing a strong rationale for targeting ET-1 receptors. This review describes the most up-to-date preclinical and clinical results obtained by using ET-1 therapeutics. The previous negative clinical results of ET-1 therapeutics should not prevent us from setting the standard of this class of drugs for future well-designed clinical trials. The preclinical data obtained with the dual ET AR and ETBR antagonist macitentan indicate that this molecule, which targets cancer cells and tumor-associated microenvironmental elements, could be a cancer therapeutic option. The field of ET-1 therapeutics will be improved in the next decade, facilitated by the new knowledge on the genomic landscape of the human stroma and tumor, and by the low invasive approaches based on liquid biopsies for the discovery of predictive biomarkers. The information obtained from preclinical studies in patient-derived models and from the Cancer Genome Atlas will set the scene of precision medicine for cancer. Results from these studies are expected to open the possibility that ET-1R antagonists might be more efficacious as molecular cancer therapeutics, able to hamper the functional ␤-arr1-dependent signaling complexes, either alone or coupled with new targeted approaches.␤-arrestin; cancer; endothelin-1; endothelin-1 receptor; target therapy RECENT INVESTIGATIONS have consistently suggested that endothelin-1 (ET-1), a small bioactive peptide of 21 residues derived from longer prepro-ET-1 precursor, is an important signal messenger in different pathological conditions, including human cancers (24,35). ET-1 belongs to a family of closely related peptides that include ET-2 and ET-3, which are all similar in structure to ET-1, but are separate gene products, with tissue-specific expression. ETs act mainly via G protein-coupled receptors (GPCR) from endothelin receptor type A (ET A R) and B (ET B R) (24). The two receptors can be differentiated by agonists and antagonists binding affinity and in their cellular distributions. The ET A R binds ET-1 with the greatest affinity, whereas ET-1, ET-2, and ET-3 all have equal affinity for the ET B R.It is now well known that ET-1 receptors can activate several signaling pathways in a G protein-independent manner via complexes with ␤-arrestin (␤-arr)-1 or -2 (18, 24). The scaffold protein ␤-arr1 serves as a copilot in ET-1 signaling to organize complex networks driving tumor progression (7,23,25,26,28,30,33). Thus ET-1 axis confers pleiotropic effects on both tumor cells and microenvironment, modulating different processes by activating ␤-arr-mediated pathways (Fig. 1A). A lesson learned from various tumor models is that there are different expression profiles of the ET-1 receptors compared with normal tissues. There are cancers expres...

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Section: Role Of Et-1 In the Interactions Of Tumor Cells With The Micmentioning

confidence: 99%

Endothelin therapeutics in cancer: Where are we?

Rosanò¹,

Bagnato²

2016

American Journal of Physiology-Regulatory, Integrative and Comp

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“…In this regard, HIF-1α/VEGF signaling has been considered as a downstream transduction pathway activated by the ET-1 axis (62). For instance, in human chondrosarcoma cells, ET-1 promoted the expression of VEGF, angiogenesis, and cell migration by activating integrin-linked kinase (ILK), Akt, and HIF-1α-mediated signaling cascades (63). In ovarian carcinoma, in both normoxic and hypoxic conditions, ET-1 induced the transcription and accumulation of HIF-1α and the upregulation of VEGF, suggesting that ET-1 action may be linked to hypoxia and HIF-1α-dependent angiogenesis (64).…”

Section: Gpcr Involvement In Tumor Angiogenesis Upon Hypoxiamentioning

confidence: 99%

Recent Advances on the Role of G Protein-Coupled Receptors in Hypoxia-Mediated Signaling

Lappano

Rigiracciolo

Marco

et al. 2016

AAPS J

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Abstract. G protein-coupled receptors (GPCRs) are cell surface proteins mainly involved in signal transmission; however, they play a role also in several pathophysiological conditions. Chemically heterogeneous molecules like peptides, hormones, lipids, and neurotransmitters activate second messengers and induce several biological responses by binding to these seven transmembrane receptors, which are coupled to heterotrimeric G proteins. Recently, additional molecular mechanisms have been involved in GPCR-mediated signaling, leading to an intricate network of transduction pathways. In this regard, it should be mentioned that diverse GPCR family members contribute to the adaptive cell responses to low oxygen tension, which is a distinguishing feature of several illnesses like neoplastic and cardiovascular diseases. For instance, the G protein estrogen receptor, namely G protein estrogen receptor (GPER)/GPR30, has been shown to contribute to relevant biological effects induced by hypoxia via the hypoxia-inducible factor (HIF)-1α in diverse cell contexts, including cancer. Likewise, GPER has been found to modulate the biological outcome of hypoxic/ischemic stress in both cardiovascular and central nervous systems. Here, we describe the role exerted by GPCR-mediated signaling in low oxygen conditions, discussing, in particular, the involvement of GPER by a hypoxic microenvironment.

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“…[30] Nowadays, compounds screened to inhibit tumor angiogenesis are provided with antitumor metastasis effects. Some models not only can be observed from histomorphology, [42] but also there are some neovascularization-related epithelial cell promoting factors, such as EGF, [43] VEGF, [44] FGF-2, [45] platelet-derived growth factor (PDGF), [46] platelet derived-endothelial cell growth factor-thymidine phosphorylase (PD-ECGF/TP) [47] and endothelin, [48] among which VEGF presents the most significant promoting effects on new vessels epithelial cells. [49] Normal epithelial cells can secrete these cell factors and so do some tumor cells.…”

Section: Cell Motility and Tumor Angiogenesismentioning

confidence: 99%

Role of traditional chinese medicine and its chemical components in anti-tumor metastasis

Zhang

2014

J Can Res Ther

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Tumor incidence has become higher and higher in recent years, and it has also become the first killer jeopardizing human health. Tumor metastasis is the major barrier for tumor treatment. Some metastases occur in 5 or 10 years and some even in 20 years after tumor is controlled, but the metastases are impossible to defend effectively till now. Therefore, controlling tumor metastasis is critical in determining tumor patients' outcomes. In consideration of the limitations, toxicity and side effects of chemotherapeutic drugs for antitumor metastasis at present stage, seeking for drugs among traditional Chinese medicines (TCM) that share high safety and can effectively prevent and control metastasis is being paid more and more attention. This article is to expound the mechanisms of tumor metastasis and summarize the researches on antitumor metastasis with TCM.

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Endothelin-1 promotes vascular endothelial growth factor-dependent angiogenesis in human chondrosarcoma cells

Cited by 95 publications

References 37 publications

Endothelin therapeutics in cancer: Where are we?

Endothelin therapeutics in cancer: Where are we?

Recent Advances on the Role of G Protein-Coupled Receptors in Hypoxia-Mediated Signaling

Role of traditional chinese medicine and its chemical components in anti-tumor metastasis

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