Clinical Significance of Circulating Osteopontin Levels in Patients With Lung Cancer and Correlation With VEGF and MMP-9

Kerenidi, Theodora; Kazakou, Aikaterini; Lada, Martha; Tsilioni, Irini; Daniil, Zoe; Gourgoulianis, Konstantinos

doi:10.1080/07357907.2016.1223301

Cited by 12 publications

(10 citation statements)

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“…After binding to its receptors, VEGF can accelerate endothelial cell division, increase production of blood vessels and lymphatic vessels, so as to promote growth, infiltration and metastasis the tumor cells ( 10 – 12 ). In recent years, VEGF has become a new target for the inhibition of tumor vascularization ( 13 ). Some studies have shown that expression levels of VEGF, carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) in the serum were positively correlated with cancer stage ( 14 ).…”

Section: Discussionmentioning

confidence: 99%

Efficacy of radiotherapy on intermediate and advanced lung cancer and its effect on dynamic changes of serum vascular endothelial growth factor and matrix metalloproteinase‑9

2018

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The present study intended to investigate efficacy of radiotherapy in the treatment of intermediate and advanced stage lung cancer and the effects on serum vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9). Serum levels of VEGF and MMP-9 of 77 patients with intermediate or advanced lung cancer were detected before and after the treatment. At the same time, 19 healthy people were selected as the control group. Gelatin zymography was applied to measure the activity of serum MMP-9, ELISA was performed to detect the VEGF and MMP-9 levels in the peripheral blood and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to measure the messenger RNA (mRNA) levels of VEGF and MMP-9 in serum. Results indicated that the overall response rate of radiotherapy on intermediate and advanced lung cancer reached 70.1%. Levels of serum VEGF and MMP-9 in the effective treatment group were significantly lower than those before the treatment (P<0.05). Furthermore, expression levels of VEGF and MMP-9 in the effective radiotherapy group were significantly lower than those in ineffective group (P<0.05), MMP-9 activity before treatment was significantly higher than that after treatment (P<0.05) and expression levels of VEGF and MMP-9 mRNA before treatment were significantly elevated compared with those after treatment (P<0.05). The results suggested that the expression levels of serum VEGF and MMP-9 may be useful indicators for the evaluation of the efficacy of radiotherapy in the treatment of intermediate and advanced lung cancer.

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Section: Discussionmentioning

confidence: 99%

Efficacy of radiotherapy on intermediate and advanced lung cancer and its effect on dynamic changes of serum vascular endothelial growth factor and matrix metalloproteinase‑9

2018

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“…In additon, through the Ras/Raf/MEK/ERK signalling pathway, an OPN-integrin complex and subsequent induction of AP-1-dependent gene expression, urokinase-type plasminogen activator (uPA) and matrix metalloproteinases (MMPs) confer a metastatic phenotype on some cancer cell types (27–29). Induced by vascular endothelial growth factor (VEGF), OPN and certain integrins are able to promote angiogenesis through enhanced endothelial cell migration, proliferation and the subsequent formation of capillaries, which are all essential requirements for the process of angiogenesis (30,31). …”

Section: Introductionmentioning

confidence: 99%

Human osteopontin: Potential clinical applications in cancer (Review)

Hao

Cui

Owen

et al. 2017

International Journal of Molecular Medicine

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Abstract. Human osteopontin (OPN) is a glycosylated phosphoprotein which is expressed in a variety of tissues in the body. In recent years, accumulating evidence has indicated that the aberrant expression of OPN is closely associated with tumourigensis, progression and most prominently with metastasis in several tumour types. In this review, we present the current knowledge on the expression profiles of OPN and its main splice variants in human cancers, as well as the potential implications in patient outcome. We also discuss its putative clinical application as a cancer biomarker and as a therapeutic target. IntroductionOsteopontin (OPN) is a bone associated, extracellular matrix glycosylated phosphoprotein which is produced by several cell types, including osteoblasts, osteoclasts, immune cells, endothelial cells, epithelial cells and extra-osseous cells (skin, kidney and lung) (1-3). Due to differences in post-translational modification (PTM) (phosphorylation, glycosylation, sulfation and proteolysis) from different cellular sources, OPN has a molecular weight ranging from 41 to 75 kDa, which may have a cell type-specific structure and function (4-7). OPN plays a major role in various normal physiological processes, including bone remodelling, immune-regulation, inflammation and vascularisation (8,9). In addition, OPN has also been shown to be involved in carcinogenesis with multi-functional activities (10)(11)(12).OPN is involved in a series of biological functions through interactions with different integrins and CD44. Therefore, OPN is classified as a member of the ʻsmall integrin-binding ligand N-linked glycoproteins' (SIBLINGs) together with other molecules, including bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP) and matrix extracellular phosphoglycoprotein (MEPE) (13). Two critical integrin binding sequences of OPN have been identified: arginine-glycine-aspartic acid (RGD) and serine-valine-valinetyrosine-glutamate-leucine-arginine (SVVYGLR). OPN interacts mainly with various αv (particularly αvβ1, αvβ3, αvβ5) integrin receptors via the classical RGD sequence, and interacts with α9β1, α4β1, α4β7 via SVVYGLR (14-16). In addition, it also interacts with the CD44 splice variants, CD44v3, CD44v6 and CD44v7, via the C-terminal fragment calcium binding site (17)(18)(19)(20). These properties of OPN induce the activation of signal transduction pathways, leading to cell proliferation, adhesion, invasion and migration, which have been demonstrated by both in vitro and in vivo models (21-23). The binding of OPN to integrins and CD44 initiates a downstream signalling cascade via the PI3K/AKT signalling pathway leading to NF-κB mediated cell proliferation and survival (24)(25)(26). In additon, through the Ras/Raf/MEK/ERK signalling pathway, an OPN-integrin complex and subsequent induction of AP-1-dependent gene expression, urokinase-type plasminogen activator (uPA) and matrix metalloproteinases (MMPs) confer a metastatic phenotype on some cancer cell types (27)(28)(29...

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“…Xia et al proposed that Midkine was a serum and urinary biomarker for the screening and prognostic scoring of NSCLC . Kerenidi et al demonstrated that the multifunctional cytokine, Osteopontin, was positively correlated with both VEGF and MMP‐9 and might serve as a prognostic biomarker in lung cancer . Bae et al found the down‐regulation of SerpinB2 in NSCLC and uncovered its prospective role as a novel biomarker for acquired gefitinib resistance and a potential target for therapeutic exploitations .…”

Section: Discussionmentioning

confidence: 99%

Serous IFNA3 predicts unfavorable prognosis in lung cancer via abnormal activation of AKT signaling

Cong

2019

IUBMB Life

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This study addresses the demand through datamining The Cancer Genome Atlas (TCGA) database and elucidates mechanistic involvements of interferon alpha 8 (IFNA8) in lung cancer. The overall survival and disease-free survival of lung cancer patients in respect to IFNA8 expression level were analyzed. IFNA8 expression levels in both serum and tumor tissue were determined by real-time polymerase chain reaction. The diagnostic value of serous IFNA8 in lung cancer was assessed by receiver operating characteristic (ROC) curve analysis. Cell viability and proliferation were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Cell Counting Kit-8 assays. in vivo pro-tumor effect of IFNA8 was evaluated using xenograft tumor model. The metastasis-prone behaviors were determined by Transwell chamber assay and tail vein-injection in mice. Protein levels of p-AKT, total AKT, and endogenous reference actin were analyzed by western blot. We uncovered high IFNA8 associated with unfavorable overall survival and disease-free survival in lung cancer patients from TCGA. We further characterized the aberrant over-expression of IFNA8 in both peripheral blood and solid tumor from our clinical patient panel, and ROC analysis suggested its potential diagnostic value. Ectopic over-expression of IFNA8 promoted viability and proliferation in both A549 and H1299 cells in vitro and accelerated xenograft tumor growth in vivo. Furthermore, IFNA8 facilitated migration, invasion, and metastasis of A549 cells in vivo. Mechanistically, we disclosed the over-activation of AKT signaling in IFNA8-proficient A549 cells, inhibition of which completely abolished the pro-tumor effects of IFNA8. We have identified IFNA8 as a novel biomarker for either diagnostic or prognostic purpose in lung cancer, which is mechanistically associated with abnormal activation of AKT signaling. K E Y W O R D SAKT signaling, biomarker, IFNA8, lung cancer

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Clinical Significance of Circulating Osteopontin Levels in Patients With Lung Cancer and Correlation With VEGF and MMP-9

Cited by 12 publications

References 38 publications

Efficacy of radiotherapy on intermediate and advanced lung cancer and its effect on dynamic changes of serum vascular endothelial growth factor and matrix metalloproteinase‑9

Efficacy of radiotherapy on intermediate and advanced lung cancer and its effect on dynamic changes of serum vascular endothelial growth factor and matrix metalloproteinase‑9

Human osteopontin: Potential clinical applications in cancer (Review)

Serous IFNA3 predicts unfavorable prognosis in lung cancer via abnormal activation of AKT signaling

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