Urocortin's Inhibition of Tumor Growth and Angiogenesis in Hepatocellular Carcinoma via Corticotrophin-Releasing Factor Receptor 2

Wang, Juejin; Xu, Youhua; Xu, Yinyan; Zhu, Huayuan; Zhang, Rongjian; Zhang, Guoxin; Li, Shengnan

doi:10.1080/07357900701788106

Cited by 45 publications

(40 citation statements)

References 24 publications

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“…For instance, Ucn inhibited angiogenesis through activation of CRF 2 receptor and subsequently suppressed the growth of hepatocellular carcinoma as well as small cell lung carcinoma cells. 54,55 Moreover, almost complete loss of CRF 2 expression in hypervascularized renal cell carcinoma supported an idea of CRF 2 as an endogenous inhibitor of angiogenesis. 56 Similarly, loss of CRF 2 receptor expression was observed in vascular endothelial cells of prostate cancer tissue not in normal prostate tissue.…”

Section: 51mentioning

confidence: 72%

Multi-facets of Corticotropin-releasing Factor in Modulating Inflammation and Angiogenesis

2015

J Neurogastroenterol Motil

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The family of corticotropin-releasing factor (CRF) composed of 4 ligands including CRF, urocortin (Ucn) 1, Ucn2, and Ucn3 is expressed both in the central nervous system and the periphery including the gastrointestinal tract. Two different forms of G protein coupled receptors, CRF1 and CRF2, differentially recognize CRF family members, mediating various biological functions. A large body of evidence suggests that the CRF family plays an important role in regulating inflammation and angiogenesis. Of particular interest is a contrasting role of the CRF family during inflammatory processes. The CRF family can exert both proand anti-inflammatory functions depending on the type of receptors, the tissues, and the disease phases. In addition, there has been a growing interest in a possible role of the CRF family in angiogenesis. Regulation of angiogenesis by the CRF family has been shown to modulate endogenous blood vessel formation, inflammatory neovascularization and cardiovascular function. This review outlines the effect of the CRF family and its receptors on 2 major biological events: inflammation and angiogenesis, and provides a possibility of their application for the treatment of inflammatory vascular diseases.

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Section: 51mentioning

confidence: 72%

Multi-facets of Corticotropin-releasing Factor in Modulating Inflammation and Angiogenesis

2015

J Neurogastroenterol Motil

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“…78 These data suggested a receptor-mediated paracrine involvement in local inflammatory phenomena within the liver. Furthermore, an antitumor effect of Ucn in HCC and in tumors growing in rodents has been demonstrated, via activation of CRF2, which inhibited cell growth and angiogenesis, 101 whereas a CRFbased apoptosis-regulating mechanism was shown in obstructive jaundice challenged liver, but not under basal conditions (Table 1). 76 These findings, although limited, advocate a potential regulatory role of the CRF system in the liver, regarding immunological functions, apoptotic mechanisms as well as oncogenic, antitumor and neoangiogenic processes.…”

Section: Future Prospectsmentioning

confidence: 99%

“…[97][98][99][100] These antitumor findings were also tested in a study showing a role of hepatic CRF receptors on tumor growth and angiogenesis. 101 Both in vivo and in vitro effects of Ucn1 were evaluated in human hepatoma cell lines SMMC-7721 and HepG2, human umbilical vein endothelial cells (HUVECs) and human hepatocellular carcinoma tissues. Ucn 1 inhibited the growth of hepatocellular carcinoma and reduced tumor microvessel density in nude mice.…”

mentioning

confidence: 99%

The corticotropin releasing factor system in the liver: expression, actions and possible implications in hepatic physiology and pathology

Paschos¹,

Chouridou²,

Koureta³

et al. 2013

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The corticotropin-releasing factor (crF) system plays a crucial regulatory role in the adaptation to exogenous and endogenous stress stimuli, as well as homeostasis. Apart from the central nervous system (cNs), the members of this neuropeptide family extend their actions in the periphery, where they may affect various body systems independently, stimulating peripheral crF receptors via vagal and/or autocrine/paracrine pathways. Here, we review all findings concerning the expression and role of the crF system in human liver, but also in other species. Direct and indirect regulatory data are also analyzed in order to draw conclusions about possible physiological/pathophysiological implications. Although data supporting any clinical significance are still limited and further research in the field is necessary, scientific interest in the crF system is particularly active, with multiple ongoing clinical studies evaluating the activity of crF ligands in medical conditions involving other organs. Thus, new knowledge with therapeutic potential appears to be steadily accumulating.

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“…Recently, increased interest has been developing in the expression and biological role of the CRH system in malignant tumors. Several lines of evidence have indicated that CRH inhibited human endometrial adenocarcinoma cell growth (Graziani et al 2002) and that Ucn1 inhibited hepatocellular carcinoma growth and angiogenesis (Bale et al 2002, Wang et al 2008. Rassouli et al (2011) suggested that dermal fibroblasts, deficient in CRH (CRHK/K), had higher proliferation and migration rates compared with WT (CRHC/C) cells.…”

Section: Introductionmentioning

confidence: 99%

Corticotropin-releasing hormone receptors mediate apoptosis via cytosolic calcium-dependent phospholipase A2 and migration in prostate cancer cell RM-1

Jin¹,

Li²,

Li³

et al. 2014

Journal of Molecular Endocrinology

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Peripheral corticotropin-releasing hormone receptors (CRHRs) are G protein-coupled receptors that play different roles depending on tissue types. Previously, we discovered the mechanism of CRHR-mediated apoptosis of mouse prostate cancer cell line (RM-1) to be a change of Bcl-2:Bax ratio, and CRH was found to inhibit transforming growth factor b migration of breast cancer cells via CRHRs. In the present study, we investigated cytosolic calcium-dependent phospholipase A 2 (cPLA 2 ) bridging CRHR activations and Bcl-2:Bax ratio and the effect of CRHR activation on cell migration. Silencing of cPLA 2 attenuated a CRHR1 agonist, CRH-induced apoptosis, and the decrease of the Bcl-2:Bax ratio, whereas silencing of cPLA 2 aggravated CRHR2 agonist, Urocortin 2 (Ucn2)-inhibited apoptosis, and the increase of the Bcl-2:Bax ratio. CRH in a timeand concentration-dependent manner increased cPLA 2 expression mainly through interleukin 1b (IL1b) upregulation. Ucn2 decreased cPLA 2 expression through neither tumor necrosis factor a nor IL1b. CRH-suppressed decay of cPLA 2 mRNA and Ucn2 merely suppressed its production. Overexpression of CRHR1 or CRHR2 in HEK293 cells correspondingly upregulated or downregulated cPLA 2 expression after CRH or Ucn2 stimulation respectively. In addition, both CRH and Ucn2 induced migration of RM-1 cells. Our observation not only established a relationship between CRHRs and cell migration but also for the first time, to our knowledge, demonstrated that cPLA 2 participates in CRHR1-induced apoptosis and CRHR2-inhibited apoptosis.

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Urocortin's Inhibition of Tumor Growth and Angiogenesis in Hepatocellular Carcinoma via Corticotrophin-Releasing Factor Receptor 2

Cited by 45 publications

References 24 publications

Multi-facets of Corticotropin-releasing Factor in Modulating Inflammation and Angiogenesis

Multi-facets of Corticotropin-releasing Factor in Modulating Inflammation and Angiogenesis

The corticotropin releasing factor system in the liver: expression, actions and possible implications in hepatic physiology and pathology

Corticotropin-releasing hormone receptors mediate apoptosis via cytosolic calcium-dependent phospholipase A2 and migration in prostate cancer cell RM-1

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