COX‐2‐Mediated Regulation of VEGF‐C in Association With Lymphangiogenesis and Lymph Node Metastasis in Lung Cancer

Liu, Huidong; Yang, Yanmei; Xiao, Jianbing; Lv, Yanhong; Liu, Yan; Yang, Huiqi; Zhao, Luqing

doi:10.1002/ar.21240

Cited by 29 publications

(19 citation statements)

References 38 publications

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“…In addition, the molecular mechanisms underlying the impact of COX-2 on BC metastasis to regional lymph node remain largely unknown. The present studies indicate that COX-2 mediates VEGF-C expression depending on the endogenous PGE2 pathway regulated by the EP1/EP4 receptors, which may contribute to tumor lymphangiogenesis and lymph node metastasis [22, 43]. All the same, more studies are required to analyze the specific molecular mechanism of COX-2 overexpression facilitating breast cancer growth and metastasis.…”

Section: Discussionmentioning

confidence: 97%

Clinicopathological and prognostic significance of COX-2 immunohistochemical expression in breast cancer: a meta-analysis

Chao

et al. 2016

Oncotarget

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The prognostic significance of COX-2 in patients with breast cancer remains controversial. The aims of our meta-analysis are to evaluate its association with clinicopathological characteristics and prognostic value in patients with breast cancer. PubMed, EMBASE, Web of Science, the Ovid Database and Grey literature were systematically searched up to May 2016. Twenty-one studies including 6739 patients with breast cancer were analyzed. The meta-analysis indicated that the incidence difference of COX-2 expression was significant when comparing the lymph node positive group to negative group (OR = 1.76, 95% CI [1.30, 2.39]) and the tumor size ≥ 2cm group to the tumor size < 2cm group (OR = 1.71, 95% CI [1.22, 2.39]). None of other clinicopathological parameters such as the ER status, PR status, HER2 status and the vascular invasion status were associated with COX-2 overexpression. The detection of COX-2 was significantly correlated with the disease-free survival (DFS) of patients (HR = 1.58, 95% CI [1.23, 2.03]) and the overall survival (OS) of patients (HR = 1.51, 95% CI [1.31, 1.72]). Our meta-analysis demonstrates that the presence of high levels of COX-2 is associated with poor prognosis for breast cancer patients and predicts bigger tumor size and lymph node metastasis.

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Section: Discussionmentioning

confidence: 97%

Clinicopathological and prognostic significance of COX-2 immunohistochemical expression in breast cancer: a meta-analysis

Chao

et al. 2016

Oncotarget

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“…The actions of PGE2 via the EP3 receptor include the promotion of platelet aggregation (44), pulmonary vasoconstriction (45), matrix metallopeptidase 9 (MMP-9) and vascular endothelial growth factor (VEGF) production (46), and the formation of pulmonary edema (39). EP4 mediates the induction of monocyte chemotactic protein-1 (MCP-1) (47), VEGF (48), and IL-6 production by macrophages (49) in response to PGE2. Because EP3 and EP4 have the highest binding affinities for PGE2 and the widest expression in the lung, their effects tend to predominate and may explain our reported findings.…”

Section: Discussionmentioning

confidence: 99%

The Role of Cyclooxygenase-2 in Mechanical Ventilation–Induced Lung Injury

Robertson

Sauer

Gold

et al. 2012

Am J Respir Cell Mol Biol

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Mechanical ventilation is necessary for patients with acute respiratory failure, but can cause or propagate lung injury. We previously identified cyclooxygenase-2 as a candidate gene in mechanical ventilationinduced lung injury. Our objective was to determine the role of cyclooxygenase-2 in mechanical ventilation-induced lung injury and the effects of cyclooxygenase-2 inhibition on lung inflammation and barrier disruption. Mice were mechanically ventilated at low and high tidal volumes, in the presence or absence of pharmacologic cyclooxygenase-2-specific inhibition with 3-(4-methylsulphonylphenyl)-4-phenyl-5-trifluoromethylisoxazole (CAY10404). Lung injury was assessed using markers of alveolar-capillary leakage and lung inflammation. Cyclooxygenase-2 expression and activity were measured by Western blotting, real-time PCR, and lung/plasma prostanoid analysis, and tissue sections were analyzed for cyclooxygenase-2 staining by immunohistochemistry. High tidal volume ventilation induced lung injury, significantly increasing both lung leakage and lung inflammation relative to control and low tidal volume ventilation. High tidal volume mechanical ventilation significantly induced cyclooxygenase-2 expression and activity, both in the lungs and systemically, compared with control mice and low tidal volume mice. The immunohistochemical analysis of lung sections localized cyclooxygenase-2 expression to monocytes and macrophages in the alveoli. The pharmacologic inhibition of cyclooxygenase-2 with CAY10404 significantly decreased cyclooxygenase activity and attenuated lung injury in mice ventilated at high tidal volume, attenuating barrier disruption, tissue inflammation, and inflammatory cell signaling. This study demonstrates the induction of cyclooxygenase-2 by mechanical ventilation, and suggests that the therapeutic inhibition of cyclooxygenase-2 may attenuate ventilator-induced acute lung injury. Keywords: cyclooxygenase-2; mechanical ventilation; lung injuryMechanical ventilation is a life-saving therapy for patients with acute respiratory failure. However, it can cause or worsen lung injury, particularly at larger tidal volumes (1, 2). Positive-pressure mechanical ventilation may expose the lungs, and particularly the alveoli, to overdistention, resulting in volutrauma with the subsequent release of inflammatory and vasoactive cytokines and prostanoids that propagate lung injury (1, 3). Therapeutic trials aimed at decreasing lung injury have focused on minimizing the damage from mechanical ventilation with the use of "protective" low tidal volume ventilator strategies. However, because of the heterogeneity of lung injury, even at lower tidal volumes, different regions of the lung may be subjected to higher stretch (4). Although using lower tidal volumes decreases markers of injury and inflammation and significantly improves survival in patients with acute lung injury, mortality remains high (1). A better understanding of the mechanisms by which mechanical ventilation injures the lungs will be key in identifying ...

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“…It was well documented that phosphatidylinositide 3-kinases (PI3K)/Akt [48, 49] and cyclooxygenase 2 (COX-2) [50, 51] are closely associated with metastasis. Here, EEOS effectively suppressed the expression of PI3K and COX-2 and the phosphorylation of Akt at protein level in OPN treated NCI-H460 cells, indicating that inhibition of PI3K/Akt and COX-2 pathway mediates anti-metastatic effect of EEOS in NCI-H460 cells.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effect of ethanol extract of Ocimum sanctum on osteopontin mediated metastasis of NCI-H460 non-small cell lung cancer cells

Kwak

Sohn

Kim

et al. 2014

BMC Complement Altern Med

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BackgroundOsteopontin (OPN) is one of important molecular targets in cancer progression, metastasis as a calcium-binding, extracellular-matrix-associated protein of the small integrin-binding ligand and, N-linked glycoprotein. In the present study, anti-metastatic mechanism of ethanol extracts of Ocimum sanctum (EEOS) was elucidated on OPN enhanced metastasis in NCI-H460 non- small cell lung cancer cells.MethodsCell viability was measured by MTT assay. Adhesion and invasion assays were carried out to see that EEOS inhibited cell adhesion and invasion in OPN treated and non-treated NCI-H 460 cells. RT-PCR was used to determine the mRNA levels of uPA, uPAR, and EGFR.ResultsEEOS significantly inhibited cell adhesion and invasion in OPN treated and non treated NCI-H460 cells, though EEOS did not show any toxicity up to 200 μg/ml. EEOS effectively attenuated the expression of OPN and CD44 and also OPN activated the expression of CD44 in NCI-H460 cells. In addition, EEOS effectively suppressed the expression of phosphatidylinositide 3-kinases (PI3K) and cyclooxygenase 2 (COX-2) and the phosphorylation of Akt at protein level in OPN treated NCI-H460 cells. Also, EEOS significantly attenuated the expression of urokinase plasminogen activator (uPA), its receptor (uPAR) and epidermal growth factor receptor (EGFR) at mRNA level and reduced vascular endothelial growth factor (VEGF) production and MMP-9 activity in OPN treated NCI-H460 cells. Furthermore, PI3K/Akt inhibitor LY294002 enhanced anti-metastatic potential of EEOS to attenuate the expression of uPA and MMP-9 in OPN treated NCI-H 460 cells.ConclusionOverall, our findings suggest that anti-metastatic mechanism of EEOS is mediated by inhibition of PI3K/Akt in OPN treated NCI-H460 non-small cell lung cancer cells.

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COX‐2‐Mediated Regulation of VEGF‐C in Association With Lymphangiogenesis and Lymph Node Metastasis in Lung Cancer

Cited by 29 publications

References 38 publications

Clinicopathological and prognostic significance of COX-2 immunohistochemical expression in breast cancer: a meta-analysis

Clinicopathological and prognostic significance of COX-2 immunohistochemical expression in breast cancer: a meta-analysis

The Role of Cyclooxygenase-2 in Mechanical Ventilation–Induced Lung Injury

Inhibitory effect of ethanol extract of Ocimum sanctum on osteopontin mediated metastasis of NCI-H460 non-small cell lung cancer cells

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