Plasma Osteopontin Levels Research Articles

Antibody-mediated molecular-targeted therapy for adult T-cell leukemia: recent progress and future challenges in the treatment of cancers

The role of the secreted matricellular molecule osteopontin (OPN) and its receptor integrins in the pathogenesis of adult T-cell leukemia (ATL) and the possible applications of an anti-OPN monoclonal antibody (mAb) for ATL immunotherapy in NOD/Shi- scid , IL-2R g null (NOG) mice were investigated. Subcutaneous inoculation of ATL cell lines into NOG mice led to increased plasma levels of OPN, correlating well with metastasis of the inoculated cells and survival time. This result suggested that the xenograft NOG mouse model could be a useful system for in vivo assessment of the physiological role of OPN in ATL pathogenesis. Intraperitoneal administration of an anti-OPN mAb resulted in the inhibition of tumor growth, tumor invasion, and metastasis. In addition, the mAb treatment led to reduction in the number of fibroblasts expressing fibroblast activation protein. We have shown here a novel mAb-mediated therapeutic strategy targeting the interaction between OPN from stromal cells and integrins on the tumors of ATL patients. In this editorial research highlight, we also comment on the recent progress in the development of mAbs and their advanced counterparts, the antibody-drug conjugate, for the treatment of cancers.

Osteopontin: A non-invasive parameter of portal hypertension and prognostic marker of cirrhosis.

To investigate the relationship between osteopontin plasma concentrations and the severity of portal hypertension and to assess osteopontin prognostic value. A cohort of 154 patients with confirmed liver cirrhosis (112 ethylic, 108 men, age 34-72 years) were enrolled in the study. Hepatic venous pressure gradient (HVPG) measurement and laboratory and ultrasound examinations were carried out for all patients. HVPG was measured using a standard catheterization method with the balloon wedge technique. Osteopontin was measured using the enzyme-linked immunosorbent assay (ELISA) method in plasma. Patients were followed up with a specific focus on mortality. The control group consisted of 137 healthy age- and sex- matched individuals. The mean value of HVPG was 16.18 ± 5.6 mmHg. Compared to controls, the plasma levels of osteopontin in cirrhotic patients were significantly higher (P < 0.001). The plasma levels of osteopontin were positively related to HVPG (P = 0.0022, r = 0.25) and differed among the individual Child-Pugh groups of patients. The cut-off value of 80 ng/mL osteopontin distinguished patients with significant portal hypertension (HVPG above 10 mmHg) at 75% sensitivity and 63% specificity. The mean follow-up of patients was 3.7 ± 2.6 years. The probability of cumulative survival was 39% for patients with HVPG > 10 mmHg and 65% for those with HVPG ≤ 10 mmHg (P = 0.0086, odds ratio (OR), 2.92, 95% confidence interval (CI): 1.09-7.76). Osteopontin showed a similar prognostic value to HVPG. Patients with osteopontin values above 80 ng/mL had significantly lower cumulative survival compared to those with osteopontin ≤ 80 ng/mL (37% vs 56%, P = 0.00035; OR = 2.23, 95%CI: 1.06-4.68). Osteopontin is a non-invasive parameter of portal hypertension that distinguishes patients with clinically significant portal hypertension. It is a strong prognostic factor for survival.

Serum osteopontin level and common carotid artery intima-media wall thickness in psoriasis.

The association between psoriasis and cardiovascular disease is well documented, but the underlying mechanisms remain unknown. The relationship between osteopontin and psoriasis has been studied. High serum levels of osteopontin are reported in psoriasis, with increased cardiovascular risk factors in these patients. We evaluate the extent of subclinical atherosclerosis by measuring the mean intima-media wall thickness (MIMT) of the common carotid artery (CCA) in patients with psoriasis and assessing its correlation with osteopontin to identify vascular risk factors associated with psoriasis. Intima-media wall thickness of the CCA and plasma osteopontin were determined in 40 patients and 40 age- and sex-matched healthy control subjects. Median serum osteopontin was significantly higher in patients with psoriasis than in healthy control subjects. Mean intima-media wall thickness of the CCA was positively associated with plasma osteopontin level (r = 0.47, P < 0.0001), body mass index (r = 0.62, P < 0.0001), age (r = 0.54, P < 0.0001), total cholesterol (r = 0.54, P < 0.0001), and triglycerides (r = 0.65, P < 0.0001). This study shows higher levels of plasma osteopontin and MIMT-CCA in psoriasis patients than in healthy controls. This is the first study to show a positive correlation between plasma osteopontin and MIMT-CCA.

Utility of Plasma Osteopontin Levels in Management of Community-Acquired Pneumonia.

Osteopontin (OPN) is an essential cytokine involved in immune cell recruitment and an important regulator of inflammation. The purpose of this study was to examine differences in OPN plasma levels between before and after antibiotic treatment in hospitalized adult patients with community-acquired pneumonia (CAP). OPN levels were measured in 93 patients with CAP and 54 healthy controls using a commercial enzyme-linked immunosorbent assay (ELISA). The CURB-65, Pneumonia Severity Index (PSI), and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were used to determine the CAP severity in patients upon initial hospitalization. A decline in the number of white blood cells (WBCs) and neutrophils, and decreases in the levels of OPN and C-reactive protein (CRP) were observed after antibiotic treatment. Only the plasma level of OPN, but not CRP, was correlated with the severity of CAP based on the PSI (r = 0.514, p < 0.001), CURB-65 (r = 0.396, p < 0.001), and APACHE II scores (r = 0.473, p < 0.001). The OPN level also showed a significant correlation with the length of hospital stay (r = 0.210, p = 0.044). In conclusion, plasma level of OPN may act as diagnostic adjuvant biomarkers for CAP and further play a role in clinical assessment of the severity of CAP, which could potentially guide the development of treatment strategies.

Development of Point-of-Care Testing for Disaster-Related Infectious Diseases.

After disaster, the victims lose their safe lives and are even exposed to nature where they could suffer from animal bites and vectors followed by suffering from zoonosis or vector-born diseases. Because of the urgent need for rapid and cheap diagnosis for infectious diseases after disaster, anonymous questionnaire clarified that leptospirosis, dengue, diarrhea, and cholera were recognized as common disaster-related infections in the Philippines, while diarrhea and pneumonia were more common in Indonesia. It should also be noted that infectious disease itself such as tuberculosis associated with acquired immune deficiency syndrome in South Africa is a disaster. Thus, the possible occurrence of similar situation in Asia should be prevented. We have conducted an international collaborative research in the Philippines and Indonesia on dengue virus, leptospira and mycobacterium tuberculosis (MTB) infectious diseases. Development of point-of-care testing for molecular diagnosis and disease severity was the principal purpose of the research. Loop-mediated isothermal amplification assay, which does not require a source of electricity, was developed for leptospirosis, dengue and MTB and has been proved to be useful where resource is limited. The plasma levels of matricellular proteins, including galectin-9 and osteopontin, were found to reflect the disease severities in dengue virus and MTB infection, probably because matricellular proteins are one of the most functional extracellular proteins that are associated with inflammatory edema. The study on disaster-related infectious disease facilitates the international cooperation for development of point-of-care testing for tropical infectious diseases.

Comparison of Plasma Osteopontin Levels between Patients with Borderline Ovarian Tumours and Serous Ovarian Carcinoma

Osteopontin (OPN) is a novel biomarker of various cancers including ovarian carcinoma. OPN is a promising adjunct to a major biomarker of ovarian cancer, CA125, in diagnosis, differential diagnosis and prognosis. The aim of our study was to measure the plasma level of OPN and CA125 in patients with borderline ovarian tumours (BOTs), serous ovarian carcinoma, and controls to determine its potential role in the differential diagnosis between serous ovarian carcinoma and BOT. The plasma samples of 66 women were analysed using Luminex technology, designed to simultaneously measure multiple specific protein targets. The mean OPN plasma level for the control group was 23.3 ng/ml; for BOT 26.3 ng/ml; and for patients with serous ovarian carcinoma 59.5 ng/ml. Specifically, there was a significant difference between the OPN levels in patients with ovarian carcinoma and BOT (P &lt; 0.001) as well as controls (P &lt; 0.001). There was no difference between the mean levels of OPN in patients with BOT and the control group (P = 0.286). Using the receiver operating characteristic (ROC), we determined the utility of OPN and CA125 to differentiate between BOT and serous ovarian carcinoma. The area under the ROC curve (AUC) for OPN was 0.793 (95% confidence interval (CI) 0.669–0.917, P &lt; 0.001) and for CA125 0.766 (95% CI 0.626–0.907, P = 0.002). Based on our data, we suggest that OPN can be used as a possible differential diagnostic biomarker to distinguish between malignant serous ovarian carcinoma and BOT.

Osteopontin in relation to Prognosis following Coronary Artery Bypass Graft Surgery.

Cardiovascular events may occur even after complete revascularization in patients with coronary artery disease. We measured preoperative osteopontin (OPN) levels in 131 consecutive patients (66.5 ± 10 years old, 117 men and 14 women) with left ventricular ejection fraction of 50.7 ± 9.2% and low logistic EuroScore (3.5 ± 3.2%) undergoing elective Coronary Artery Bypass Grafting (CABG) surgery. Patients were prospectively followed up for a median of 12 months (range 11–24). The primary study endpoint was the composite of cardiovascular death, nonfatal myocardial infarction, need for repeat revascularization, and hospitalization for cardiovascular events. Pre-op OPN plasma levels were 77.9 (49.5, 150.9). Patients with prior acute myocardial infarction (AMI) had significantly higher OPN levels compared to those without [131.5 (52.2, 219) versus 73.3 (45.1, 125), p = 0.007]. OPN levels were positively related to EuroScore (r = 0.2, p = 0.031). Pre-op OPN levels did not differ between patients who had a major adverse event during follow-up compared to those with no event (p = 0.209) and had no effect on the hazard of future adverse cardiac events [HR (95% CI): 1.48 (0.43–4.99), p = 0.527]. The history of AMI was associated with increased risk of subsequent cardiovascular events at follow-up (p = 0.02). OPN is associated with preoperative risk assessment prior to low-risk CABG but did not independently predict outcome.

Osteopontin-integrin interaction as a novel molecular target for antibody-mediated immunotherapy in adult T-cell leukemia.

BackgroundAdult T-cell leukemia (ATL) is a CD4+ T-cell neoplasm with a poor prognosis. A previous study has shown that there is a strong correlation between the secreted matricellular protein osteopontin (OPN) level and disease severity in ATL patients. Here, we investigated the role of OPN in ATL pathogenesis and the possible application of anti-OPN monoclonal antibody (mAb) for ATL immunotherapy in NOD/Shi-scid,IL-2Rgnull (NOG) mice.ResultsSubcutaneous inoculation of ATL cell lines into NOG mice increased the plasma level of OPN, which significantly correlated with metastasis of the inoculated cells and survival time. Administration of an SVVYGLR motif-recognizing anti-OPN mAb resulted in inhibition not only of tumor growth but also of tumor invasion and metastasis. The number of fibroblast activating protein-positive fibroblasts was also reduced by this mAb. We then co-inoculated mouse embryonic fibroblasts (MEFs) isolated from wild-type (WT) or OPN knockout mice together with ATL-derived TL-OmI cells into the NOG mice. The mice co-inoculated with WT MEFs displayed a significant decrease in survival relative to those injected with TL-OmI cells alone and the absence of OPN in MEFs markedly improved the survival rate of TL-OmI-inoculated mice. In addition, tumor volume and metastasis were also reduced in the absence of OPN.ConclusionWe showed that the xenograft NOG mice model can be a useful system for assessment of the physiological role of OPN in ATL pathogenesis. Using this xenograft model, we found that fibroblast-derived OPN was involved in tumor growth and metastasis, and that this tumor growth and metastasis was significantly suppressed by administration of the anti-OPN mAbs. Our findings will lead to a novel mAb-mediated immunotherapeutic strategy targeting against the interaction of OPN with integrins on the tumor of ATL patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12977-015-0225-x) contains supplementary material, which is available to authorized users.

Is There a Place for Plasma Osteaopontin as Key Mediator in Patients with Diabetic Nephropathy ?

Background: micro- and macro-vasculopathies, such as nephropathy and coronary artery disease (CAD), respectively, are common in diabetes and constitute the major causes of death for in these patients. Pro-inflammatory cytokines play a critical role in the pathogenesis of diabetic complications through various biochemical and cellular pathways. Osteopontin (OPN) has been identified as a key regulator of many metabolic and inflammatory diseases including obesity, diabete and diabetic nephropathy. The aim of this study was to evaluate plasma level of osteopontin in different stages of diabetic nephropathy in type II DM, and to correlate it with the stage of nephropathy and with other measured parameters. Patients and methods:the study was conducted on 58 patients with diabetic nephropathy as well as 15 apparently healthy subjects as a control group. Patients were classified into 2 main groups according to the level of glycosylated hemoglobin (HbA1c) Group I: controlled type II DM (HbA1c 5.55%-7.6%). Group II: uncontrolled type II DM (HbA1c 7.6 %).Each group was subdivided into two subgroups (A and B) according to the presence of microalbuminuriaor macroalbuminuria (degree of nephropathy). In addition to, Group III: DM type II with end stage renal disease (serum creatinine ≥ 5mg/dl) and just starting hemodialysis (1-3 sessions Only) plasma osteopontin was measured by ELISA. Results of the study revealed significant increase of serum osteopontin in all studied groups Results: compared to normal control subjects (P 0.05).Cut ROC curve of osteopontin levels of all cases of diabetic nephropathy indicates high validity of OPN to detect positive cases of diabetic nephropathy with accuracy of 100%, andOPN is considered a high validity test in prediction of end-stage renal disease (ESRD) more than prediction of microalbumnuria. Conclusion: plasma level of osteopontin increases with the progression of diabetic nephropathy and osteopontin may be useful as a biomarker to trace disease progression as well as a potential diagnostic biomarker for the prediction of diabetic ESRD.

Schistosome-induced cholangiocyte proliferation and osteopontin secretion correlate with fibrosis and portal hypertension in human and murine schistosomiasis mansoni.

Schistosomiasis is a major cause of portal hypertension worldwide. It associates with portal fibrosis that develops during chronic infection. The mechanisms by which the pathogen evokes these host responses remain unclear. We evaluated the hypothesis that schistosome eggs release factors that directly stimulate liver cells to produce osteopontin (OPN), a pro-fibrogenic protein that stimulates hepatic stellate cells to become myofibroblasts. We also investigated the utility of OPN as a biomarker of fibrosis and/or severity of portal hypertension. Cultured cholangiocytes, Kupffer cells and hepatic stellate cells were treated with soluble egg antigen (SEA); OPN production was quantified by quantitative reverse transcriptase polymerase chain reaction (qRTPCR) and ELISA; cell proliferation was assessed by BrdU (5-bromo-2'-deoxyuridine). Mice were infected with Schistosoma mansoni for 6 or 16weeks to cause early or advanced fibrosis. Liver OPN was evaluated by qRTPCR and immunohistochemistry (IHC) and correlated with liver fibrosis and serum OPN. Livers from patients with schistosomiasis mansoni (early fibrosis n=15; advanced fibrosis n=72) or healthy adults (n=22) were immunostained for OPN and fibrosis markers. Results were correlated with plasma OPN levels and splenic vein pressures. SEA-induced cholangiocyte proliferation and OPN secretion (P<0.001 compared with controls). Cholangiocytes were OPN (+) in Schistosoma-infected mice and humans. Liver and serum OPN levels correlated with fibrosis stage (mice: r=0.861; human r=0.672, P=0.0001) and myofibroblast accumulation (mice: r=0.800; human: r=0.761, P=0.0001). Numbers of OPN (+) bile ductules strongly correlated with splenic vein pressure (r=0.778; P=0.001). S. mansoni egg antigens stimulate cholangiocyte proliferation and OPN secretion. OPN levels in liver and blood correlate with fibrosis stage and portal hypertension severity.

Endostatin and osteopontin are elevated in patients with both coronary artery disease and aortic valve calcification

BackgroundThe angiostatic factor endostatin (ES) plays an important role as mediator of angiogenesis. Elevated osteopontin (OPN) was associated with valve calcification in healthy individuals. The present study aimed to investigate ES and OPN levels in patients with both coronary artery disease (CAD) and aortic valve calcification (AVC). Methods and resultsIn total 224 non- or ex-smoking patients (161 male, mean age: 61.09±11.02years; 63 female: mean age: 67.49±7.87years) with angiographically verified and quantified CAD were recruited. Serum ES and plasma OPN levels were measured by ELISA and AVC was evaluated by a parasternal short axis view and quantified as non-, mild or moderate/severe. There was a stepwise increase of ES measurable with increasing severity of AVC, independent from age, BMI and CAD-severity (p=0.018; F=4.09). OPN also increased significantly with the grade of AVC severity (p=0.029; F=3.61) but was no longer significant when the co-variables (p=0.31; F=1.18) were inserted. ConclusionsThis is the first study showing an association of ES with AVC in CAD-patients independent from age, BMI and CAD-severity which seems to be of distinct interest when trying to understand the process of heart valve calcification. OPN also correlates with AVC-severity but is mostly dependent on the age of the patients.

Assessment of serum levels of osteopontin, selenium and prolactin in patients with psoriasis compared with healthy controls, and their association with psoriasis severity.

The association between psoriasis and cardiovascular diseases is well documented, but the underlying mechanisms remain unknown. Overexpression of osteopontin (OPN) has been reported in the plasma of patients with psoriasis, with increased cardiovascular risk factors in these patients. Selenium compounds are effective in downregulating OPN expression. We investigated the levels of OPN, selenium and prolactin (PRL) in psoriasis, and their association with metabolic status in patients to identify a possible link between these markers and observed comorbidities. Plasma samples from 40 patients with psoriasis and 40 age- and sex-matched healthy controls (HCs) were collected for ELISA. The clinical significance of plasma OPN, selenium and PRL levels in patients compared with controls was analysed in relation to metabolic disorders. There was no significant difference in median serum selenium levels between the two groups. Serum levels of PRL were not significantly different from those of HCs, but levels of OPN were significantly higher in patients with psoriasis than in HCs. High plasma OPN is a predictor for occurrence of psoriasis. Our study showed that serum selenium and PRL were not decreased in patients with psoriasis, but there was a negative statistically significant correlation between OPN and selenium in all participants.

Mechanical stretch enhances the expression and activity of osteopontin and MMP-2 via the Akt1/AP-1 pathways in VSMC

Hemodynamic forces causing mechanical stretch (MS) of vascular smooth muscle cells (VSMC) play an important role in vascular remodeling, but the underlying mechanism involved is not fully understood. Thus, this study investigated whether osteopontin (OPN) expression in VSMC was induced by MS, and identified the intracellular signaling pathways involved in OPN production. The plasma level of OPN and its expression in aortic tissue were increased in various animal models of hypertension including spontaneous hypertensive rats and hypertensive mice induced by angiotensin II or L-NAME. When aortic VSMC was stimulated with MS, OPN production was increased, which was markedly attenuated in VSMC treated with PI3K/Akt inhibitor as well as in Akt1-depleted cells, but not in Akt2-depleted cells, suggesting a pivotal role of Akt1 isoform in OPN expression in VSMC. In the promoter assay, MS increased OPN promoter activity, which was attenuated when the region harboring AP-1 binding sites was mutated. The MS-enhanced promoter activity and OPN expression were also decreased in cells treated with AP-1 siRNA or inhibitor. Moreover, MS-induced MMP-2 production was attenuated in cells treated with OPN siRNA or anti-OPN antibody as well as in OPN-deficient VSMC cultured from aorta of OPN deficient mice. In in vivo experiments, the expressions of OPN and MMP-2 were increased in the aortic tissues from hypertensive mice, but these increases were markedly attenuated in OPN-deficient mice with hypertension. In conclusion, these results suggested that OPN expression in the hypertensive vasculature was increased via signaling pathways that involve Akt1/AP-1, leading to vascular remodeling by increasing the production of MMP-2.

Post-operative plasma osteopontin predicts distant metastasis in human colorectal cancer.

BackgroundThe overall prognosis of colorectal cancer (CRC) patients is unsatisfactory due to cancer metastasis after operation. This study aims to investigate the clinical significance of plasma osteopontin (OPN) levels as minimally invasive, predictive, and surrogate biomarkers for prognosis of CRC patients.MethodsThis randomized study design consists of pre-operative and post-operative plasma samples from a total of 79 patients. We determined plasma levels of OPN by ELISA and examined their correlation with the clinicopathological parameters of CRC patients. The effects of endogenous and exogenous OPN on CRC metastasis were investigated by examination of the effect on regulators of epithelial to messenchymal transition and migration assay.ResultsOur findings demonstrated for the first time the clinical correlation of plasma OPN with metastasis of CRC patients. High post-operative plasma OPN level (>153.02 ng/ml) associated with development of metastasis after curative resection (p<0.001). Moreover, post-operative plasma OPN level correlated with disease-free survival of CRC patients (p=0.009) and was an independent factor for predicting development of metastasis in CRC patients after curative resection (p=0.036). Our in vitro model showed that OPN ectopic expression induced DLD1 cell migration through Snail and Twist1 overexpression and E-cadherin repression, and secretory OPN level enhanced cell migration.ConclusionsThe results of the current study suggest that post-operative plasma OPN correlated with post-operative metastasis, suggesting that it is a potential non-invasive biomarker for the development of future metastasis in CRC patients. In addition, OPN was shown to be involved in the metastatic process and thus inhibition of OPN is a potential therapeutic approach to treat CRC patients.

Osteopontin, CCL5 and CXCL9 are independently associated with psoriasis, regardless of the presence of obesity

Psoriasis is an autoimmune disease associated with the production of pro-inflammatory cytokines. The identification of these molecules in the pathogenesis of psoriasis facilitated the use of monoclonal antibodies to block their actions as a treatment for severe psoriasis. An increased inflammatory response has been documented in patients with obesity, a condition that is associated with the occurrence and severity of psoriasis. Osteopontin (OPN), TNF and CXCL9 levels are enhanced in patients with psoriasis, although OPN has been documented in the adipose tissue of obese patients without psoriasis. The prevalence of obesity is much higher in psoriasis patients compared with the general population. Thus, we aimed to evaluate the relationship between cytokine levels and psoriasis in the context of obesity. We compared OPN and CXCL9 plasma levels among 117 psoriasis patients and 27 healthy body mass index-matched subjects using ELISA. We also analyzed the TNF, CCL2 and CCL5 levels in a smaller subgroup of patients and matched controls. Median OPN, CCL5 and CXCL9 levels were significantly higher in psoriasis patients compared with the controls, independent of obesity. There was no difference between the median CCL2 levels in the psoriasis patients and the controls (P<0.05), although the CCL2 levels were elevated in obese patients compared with non-obese psoriasis patients (P<0.001). Facial involvement and the psoriasis area severity index (PASI) score were not associated (P<0.05) with OPN levels or elevated levels of chemokines. There was no significant correlation between the OPN and CXCL9 levels or the OPN and TNF levels in psoriasis patients. This work confirms that OPN, CCL5 and CXCL9 plasma levels are higher in psoriasis patients and provides evidence that their higher levels are not a consequence of obesity. Furthermore, the results demonstrate that OPN production is independent of TNF-α and CXCL9.

Description of cardiovascular remodeling parameters and osteopontin plasma level in dynamics of the candesartan therapy in patients with chronic kidney disease on the stage before dialysis

Aim. To examine the cardiovascular remodeling parameters and osteopontin plasma level in dynamics of the candesartan therapy in patients with chronic kidney disease on the stage before dialysis Methods and results. Peculiarities of the cardiovascular remodeling were studied in 52 patients with chronic kidney disease III, IV, and V stage. Echocardiography, carotid dopplerography, and immunoassay detection of the osteopontin level were done. The predominant type of pathological left ventricular geometry was concentric hypertrophy, its prevalence increased with worsening of the renal function. The maximum level of IMT was observed at stage V of the CKD. The chronic kidney disease progression was accompanied by increased plasma levels of the osteopontin. Conclusion. Direct correlation between the concentration of the protein and the index of left ventricular mass and the intima-media thickness were detected. The therapy with candesartan during 12 weeks leads to the significant reduction of osteopontin, which can be considered as a marker of cardiovascular remodeling in patients with CKD.

STUDY OF OSTEOPONTIN AS A NOVELTUMOR MARKER FOR DETECTION OF HEPATOCELLULAR CARCINOMA

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third most common cause of death from cancer worldwide. Approximately, 80 to 90% of HCC occur in a cirrhotic liver. HCC is now a rather common malignancy in Egypt which usually develops on top of liver cirrhosis secondary to viral infection. Hepatitis C virus increases the risk of HCC in the Egyptian patients. Osteopontin (OPN) is a glycoprotein secreted by cells as osteoblasts, osteoclasts, activated macrophages and T cells. It is over expressed in a variety of human tumors, including carcinomas of stomach, breast, prostate, lung, colon, and liver. Plasma level of osteopontin may be a biomarker for HCC. Objective: This study aimed to evaluate plasma osteopontin (OPN) level and determine its sensitivity and specificity as a screening tool for detection of HCC patients. Subjects and Methods: Plasma OPN level was measured in 64 patients(Twenty two patients with non-cirrhotic HCV, twenty two with cirrhotic HCV and twenty HCC patients on top of chronic cirrhotic HCV)in addition to twenty healthy controls. Plasma OPN level using ELISA technique was done to all participants. Also, liver enzymes (AST) and (ALT), serum bilirubin, albumin, alpha-fetoprotein and blood hemoglobin (Hb) were done to all participants. Results: The mean plasma osteopontin (OPN) level significantly elevated in patients with HCC group than all groups. The sensitivity and specificity in detection of HCC were 100% and 97% respectively at cut off level of 270 ng/ml with accuracy 95%. Conclusion: Plasma OPN level can be used as a routine biomarker for clinical prediction of the recurrence, metastasis, and prognosis in patients with HCC.

Su1906 Plasma Levels of Osteopontin Are Significantly Increased in Patients With Colorectal Cancer

Su1906 Plasma Levels of Osteopontin Are Significantly Increased in Patients With Colorectal Cancer

Intracellular Osteopontin Induced by CagA‐positive Helicobacter pylori Promotes Beta‐catenin Accumulation and Interleukin‐8 Secretion in Gastric Epithelial cells

Osteopontin, an important immune modulator and oncogenic promoter, is upregulated in H. pylori-infected gastric mucosa. However, the underlying mechanisms and biological significance are poorly understood. We investigated whether osteopontin was upregulated in gastric epithelial cells by H. pylori and the virulence factors involved. Moreover, cellular component changes caused by osteopontin were also investigated. The gastric epithelial cell line MKN45 was cocultured with wild-type and mutant H. pylori to analyze osteopontin expression. Beta-catenin levels in cell lysate and interleukin-8 levels in supernatant were analyzed. The difference in osteopontin expression levels in both gastric epithelium and plasma was compared between H. pylori-infected patients and uninfected controls. H. pylori induced intracellular, but not secretory, osteopontin expression in MKN45 cells. Accordingly, osteopontin expression intensity in gastric epithelium was higher in H. pylori-infected patients than in controls, but osteopontin levels in plasma were similar between both patient groups. H. pylori virulence factor CagA delivered via the type IV secretion system was essential for intracellular osteopontin upregulation. H. pylori induced β-catenin accumulation and interleukin-8 secretion, whereas osteopontin knockdown completely abrogated these effects, in MKN45 cells. TLR2 antagonist abolished iOPN expression induced by H. pylori gastritis strain, but not by H. pylori cancer strain. H. pylori is dependent on CagA translocation via the type IV secretion system to induce intracellular osteopontin expression in gastric epithelial cells. Upregulated intracellular osteopontin may promote gastric carcinogenesis via increased β-catenin accumulation and interleukin-8 secretion.

Prognostic significance of plasma osteopontin level in breast cancer patients

Abstract Many studies have demonstrated that osteopontin (OPN) contributes functionally to aggressive behaviour in many tumours including breast cancer. This study aims to investigate its role as a simple biochemical marker easily measured in plasma of breast cancer patients to give an early signal for metastases and to detect its relationship to clinicopathological findings and survival. We measured plasma OPN, CA15.3 and serum alkaline phosphatase (ALP) activity in 55 patients, 28 with early stage breast cancer and 27 with bone metastasis out of whom 20 had metastasis in other sites. The median age at diagnosis for non-metastatic cases was 60 years (range 35-85) and for metastatic cases was 45.5 years (range 32-59). In the non-metastatic group, 78.57% of the patients were histologically graded as grades I and II and 21.43% as grade III tumours. In the metastatic group, 81.48% of the patients had grades I and II and 18.52% had grade III tumours; 54% of patients in the non-metastatic group were at stage II and 46% were at stage III at presentation. All patients of group II had bone metastasis, 33% had liver metastases, 25.9% had lung metastasis and 14.8% had lymph node metastasis. Patients with non-metastatic disease had a median OPN level of 55 ng/ml (range 54-150 ng/l), while those in the metastatic group had a median of 148.0 ng/l (range 56.0-156.0 ng/l), a difference which was statistically significant (P = 0.001). There was no statistically significant difference in the median levels of CA15.3 and ALP between both groups. The median OPN level was significantly higher with serum ALP level above 90, progesterone receptor (PR) status, bone and visceral metastasis. Median OPN was not affected significantly by menopausal status (P-value 0.3), tumour grade (P-value 0.3), estrogen receptor (ER) status (P-value 0.7), pathological type (P-value 0.42) or serum CA15.3 level (P-value 0.6). At the end of 12-year follow-up, 83% of the patients survived (92.3% in the non-metastatic versus 74.1% in the metastatic group). The estimated median survival for the whole study population at 12 years was 13 years (95% CI 8.144-17.856). The estimated median survival was 13 years (95% CI 0) and 12 years (95% CI 4.893-19.11) in patients with median OPN levels of &lt;142 and ≥142, respectively, a difference which was not statistically significant (P = 0.343). No statistically significant difference in overall survival OS was noticed in relation to menopausal status (P = 0.7), pathological type (P = 0.4) and hormone receptor status (P = 0.3). At 6-year follow-up, it was found that OS was affected by the presence of visceral metastasis, tumour grade, serum plasma level of ALP and the serum level of CA15.3 (P = 0.0006, 0.007, 0.001 and 0.03, respectively). However, the presence of bone metastasis did not affect OS (P = 0.6). Osteopontin level can be a simple biochemical marker easily measured in plasma of breast cancer patients to give early signals for metastases, but not a prognostic factor for survival.