Thromboxane synthase expression and correlation with VEGF and angiogenesis in non-small cell lung cancer

Cathcart, Mary-Clare; Gately, Kathy; Cummins, Robert; Drakeford, Clive; Kay, Elaine W.; O’Byrne, Kenneth J.; Pidgeon, Graham P.

doi:10.1016/j.bbadis.2014.01.011

Cited by 22 publications

(19 citation statements)

References 51 publications

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“…These observations indicate that thromboxane/TP signaling likely acted as an endogenous inhibitor of ASC differentiation toward ECs under (patho)physiological conditions. However, others reported that TP blockers suppressed migration and angiogenesis of human umbilical vein ECs and human dermal microvascular ECs, 44 TxAS overexpression observed in nonsmall cell lung cancers promotes tumor growth and VEGF secretion, 45,46 and activation of TP induced the differentiation of human ASCs to smooth muscle-like cells. 47,48 The discrepancies are probably ascribed to different cells and different approaches used, and perhaps different downstream signaling is mediated by TP receptors.…”

Section: Discussionmentioning

confidence: 99%

Thromboxane Governs the Differentiation of Adipose-Derived Stromal Cells Toward Endothelial Cells In Vitro and In Vivo

Shen

Zuo

Wang

et al. 2016

Circulation Research

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Rationale: Autologous adipose-derived stromal cells (ASCs) offer great promise as angiogenic cell therapy for ischemic diseases. Because of their limited self-renewal capacity and pluripotentiality, the therapeutic efficacy of ASCs is still relatively low. Thromboxane has been shown to play an important role in the maintenance of vascular homeostasis. However, little is known about the effects of thromboxane on ASC-mediated angiogenesis. Objective: To explore the role of the thromboxane-prostanoid receptor (TP) in mediating the angiogenic capacity of ASCs in vivo. Methods and Results: ASCs were prepared from mouse epididymal fat pads and induced to differentiate into endothelial cells (ECs) by vascular endothelial growth factor. Cyclooxygenase-2 expression, thromboxane production, and TP expression were upregulated in ASCs on vascular endothelial growth factor treatment. Genetic deletion or pharmacological inhibition of TP in mouse or human ASCs accelerated EC differentiation and increased tube formation in vitro, enhanced angiogenesis in in vivo Matrigel plugs and ischemic mouse hindlimbs. TP deficiency resulted in a significant cellular accumulation of β-catenin by suppression of calpain-mediated degradation in ASCs. Knockdown of β-catenin completely abrogated the enhanced EC differentiation of TP-deficient ASCs, whereas inhibition of calpain reversed the suppressed angiogenic capacity of TP re-expressed ASCs. Moreover, TP was coupled with Gαq to induce calpain-mediated suppression of β-catenin signaling through calcium influx in ASCs. Conclusion: Thromboxane restrained EC differentiation of ASCs through TP-mediated repression of the calpain-dependent β-catenin signaling pathway. These results indicate that TP inhibition could be a promising strategy for therapy utilizing ASCs in the treatment of ischemic diseases.

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Section: Discussionmentioning

confidence: 99%

Thromboxane Governs the Differentiation of Adipose-Derived Stromal Cells Toward Endothelial Cells In Vitro and In Vivo

Shen

Zuo

Wang

et al. 2016

Circulation Research

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“…Recent studies demonstrated that TxA 2 activated the TP signaling pathway, and promoted cell proliferation, survival, and invasion [77][78][79][80]. TP also promoted tumor growth and angiogenesis via induction of VEGF in A549 cells and NSCLC patients [81,82]. NNK's oncogenic mechanisms in lung cancer ( part I) NNK, the lung cancer carcinogen, activates several signaling pathways as follows: (i) NNK increases α7-nAChR-mediated expression of contactin 1, followed by activating RhoA and down-regulating E-cadherin, thereby promoting tumor invasion and metastasis.…”

Section: Nnk Regulates Gene Expression Through Dna Methyltransferase mentioning

confidence: 99%

Tobacco carcinogen NNK-induced lung cancer animal models and associated carcinogenic mechanisms

Ge¹,

Xu²,

Chen³

2015

ABBS

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Tobacco usage is a major risk factor in the development, progression, and outcomes for lung cancer. Of the carcinogens associated with lung cancer, tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is among the most potent ones. The oncogenic mechanisms of NNK are not entirely understood, hindering the development of effective strategies for preventing and treating smoking-associated lung cancers. Here, we introduce the NNK-induced lung cancer animal models in different species and its potential mechanisms. Finally, we summarize several chemopreventive agents developed from these animal models.

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“…Nonsmall cell lung cancer (NSCLC) is one of the most life‐threatening type of lung cancer, and its development and metastasis are closely related to angiogenesis . In addition, many investigations have shown that high Plt number was significantly associated with poor prognosis in patients with advanced NSCLC .…”

Section: Introductionmentioning

confidence: 99%

The angiogenic responses induced by release of angiogenic proteins from tumor cell‐activated platelets are regulated by distinct molecular pathways

Fan

Liu

et al. 2015

IUBMB Life

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There is mounting evidence that tumor angiogenesis can be regulated by platelets (Plts), which serve as major sources and delivery vehicles of many proangiogenic cytokines including transforming growth factor-b and vascular endothelial growth factor. Although considerable progress has been made in understanding the role for Plt secretion in tumor angiogenesis, very little is known about the precise mechanisms underlying cancer cell induction of Plt granule release. Here, we demonstrated that nonsmall cell lung cancer (NSCLC) cells directly induced Plt secretion of several angiogenic regulatory cytokines that promoted angiogenesis in concert. Moreover, we discovered that these Plt-derived angiogenesis modulators were regulated by different molecular pathways and could be largely inhibited by combination of multiple signaling inhibitors. Our present studies indicated that manipulation of Plt secretion of angiogenic cytokines without compromising hemostatic functions could provide a novel option for management of tumor angiogenesis and metastasis in NSCLC patients with thrombocytosis. V C 2015 IUBMB Life, 67(8):626-633, 2015

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Thromboxane synthase expression and correlation with VEGF and angiogenesis in non-small cell lung cancer

Abstract: TXS promotes tumor growth in-vivo in NSCLC, an effect which is at least partly mediated through increased tumor angiogenesis.

Cited by 22 publications

References 51 publications

Thromboxane Governs the Differentiation of Adipose-Derived Stromal Cells Toward Endothelial Cells In Vitro and In Vivo

Thromboxane Governs the Differentiation of Adipose-Derived Stromal Cells Toward Endothelial Cells In Vitro and In Vivo

Tobacco carcinogen NNK-induced lung cancer animal models and associated carcinogenic mechanisms

The angiogenic responses induced by release of angiogenic proteins from tumor cell‐activated platelets are regulated by distinct molecular pathways

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