Modulation of Nogo receptor 1 expression orchestrates myelin-associated infiltration of glioblastoma.

As the clinical failure of glioblastoma treatment is attributed by multiple components, including myelin-associated infiltration, assessment of the molecular mechanisms underlying such process and identification of the infiltrating cells have been the primary objectives in glioblastoma research. Here, we adopted radiogenomic analysis to screen for functionally relevant genes that orchestrate the process of glioma cell infiltration through myelin and promote glioblastoma aggressiveness. The receptor of the Nogo ligand (NgR1) was selected as the top candidate through Differentially Expressed Genes (DEG) and Gene Ontology (GO) enrichment analysis. Gain and loss of function studies on NgR1 elucidated its underlying molecular importance in suppressing myelin-associated infiltration in vitro and in vivo. The migratory ability of glioblastoma cells on myelin is reversibly modulated by NgR1 during differentiation and dedifferentiation process through deubiquitinating activity of USP1, which inhibits the degradation of ID1 to downregulate NgR1 expression. Furthermore, pimozide, a well-known antipsychotic drug, upregulates NgR1 by post-translational targeting of USP1, which sensitizes glioma stem cells to myelin inhibition and suppresses myelin-associated infiltration in vivo. In primary human glioblastoma, downregulation of NgR1 expression is associated with highly infiltrative characteristics and poor survival. Together, our findings reveal that loss of NgR1 drives myelin-associated infiltration of glioblastoma and suggest that novel therapeutic strategies aimed at reactivating expression of NgR1 will improve the clinical outcome of glioblastoma patients.

Epigenetic-mediated dysfunction of the bone morphogenetic protein pathway inhibits differentiation of glioblastoma-initiating cells.

Despite similarities between tumor-initiating cells with stem-like properties (TICs) and normal neural stem cells, we hypothesized that there may be differences in their differentiation potentials. We now demonstrate that both bone morphogenetic protein (BMP)-mediated and ciliary neurotrophic factor (CNTF)-mediated Jak/STAT-dependent astroglial differentiation is impaired due to EZH2-dependent epigenetic silencing of BMP receptor 1B (BMPR1B) in a subset of glioblastoma TICs. Forced expression of BMPR1B either by transgene expression or demethylation of the promoter restores their differentiation capabilities and induces loss of their tumorigenicity. We propose that deregulation of the BMP developmental pathway in a subset of glioblastoma TICs contributes to their tumorigenicity both by desensitizing TICs to normal differentiation cues and by converting otherwise cytostatic signals to proproliferative signals.

A study on macronutrient self-selection after acute aerobic exercise in college females.

[Purpose] This study was conducted to determine whether acute aerobic exercise (climbing) is associated with changes in the dietary intake pattern. [Subjects and Methods] Food intake and physical activity data for 15 female college students were sampled for 3 days and categorized according to routine activity or high-intensity activity such as hiking. Nutrient intake based on the data was analyzed using a nutrition program. [Results] Carbohydrate and protein intake was significantly decreased after exercise compared to before acute aerobic exercise, but lipid intake showed no significant difference. Calorie intake was significantly decreased after exercise compared to before exercise; however, calorie consumption was significantly increased after exercise. [Conclusion] Aerobic exercise causes a decrease in total calories by inducing reduction in carbohydrate and protein intake. Therefore, aerobic exercise is very important for weight (body fat) control since it causes positive changes in the food intake pattern in female students.

Monetary policy document analysis for prediction of monetary policy board decision.

In terms of market capitalization, the bond market is larger than the stock market, and the bond market is affected by macroeconomic indicators. Despite this, there has been relatively little research, making it a good candidate for the use of data mining techniques. In this paper, a novel approach designed to predict the vote results of the Korean Monetary Policy Committee regarding the base interest rate was proposed. To predict sentence sentiment, prior monetary policy decision text was used as input for classification models. The sentence sentiment prediction model showed 83.7% performance when using a support vector machine. In addition, it was observed that the bigrams extracted from documents provided important descriptions of the Korean economy at the time. Finally, the document sentiment of monetary policy decision was calculated using aggregating sentence sentiment, and the vote results were predicted using this sentiment. As a result, when using the support vector machine to predict the Monetary Policy Committee vote results, the performance improved by 29.5% over the baseline model. Statistical tests confirmed whether there is a difference in document sentiments between unanimous and non-unanimous, and the null hypothesis was rejected at a significance level of 5%.

Enhanced Photoluminescence of Crystalline Alq3 Micro-Rods Hybridized with Silver Nanowires.

An enhancement of the local electric field at the metal/dielectric interface of hybrid materials due to the localized surface plasmon resonance (LSPR) phenomenon plays a particularly important role in versatile research fields resulting in a distinct modification of the electrical, as well as optical, properties of the hybrid material. In this paper, we succeeded in visually confirming the LSPR phenomenon in the crystalline tris(8-hydroxyquinoline) aluminum (Alq3) micro-rod (MR) hybridized with silver (Ag) nanowire (NW) in the form of photoluminescence (PL) characteristics. Crystalline Alq3 MRs were prepared by a self-assembly method under the mixed solution of protic and aprotic polar solvents, which could be easily applied to fabricate hybrid Alq3/Ag structures. The hybridization between the crystalline Alq3 MRs and Ag NWs was confirmed by the component analysis of the selected area electronic diffraction attached to high-resolution transmission electron microscope. Nanoscale and solid state PL experiments on the hybrid Alq3/Ag structures using a lab-made laser confocal microscope exhibited a distinct enhancement of the PL intensity (approximately 26-fold), which also supported the LSPR effects between crystalline Alq3 MRs and Ag NWs.

Wnt activation is implicated in glioblastoma radioresistance.

Glioblastoma (GBM) patients have dismal median survival even with the most rigorous treatments currently available. Radiotherapy is the most effective non-surgical therapy for GBM patients; however, patients succumb due to tumor recurrence within a year. To develop a curative therapeutic approach, we need to better understand the underlying molecular mechanism of radiation resistance in GBM. Towards this goal, we developed an in vivo orthotopic GBM model system that mimics the radiation response of human GBM, using both established-GBM cell line and patient-derived freshly dissociated GBM specimen. In-vivo ionizing radiation (IR) treatment prolonged the survival of mice with intracranical tumor derived from U373MG, but failed to prevent tumor recurrence. U373MG and GBM578 cells isolated after in-vivo IR (U373-IR and 578-IR) were more clonogenic and enriched with stem cell-like characteristics, compared with mock-treated control tumor cells. Transcriptomic analyses and quantitative real-time reverse-transcription PCR analyses using these matched GBM cells before and after radiation treatment revealed that Wnt pathways were preferentially activated in post-IR GBM cells. U373-IR cells and 578-IR were enriched with cells positive for both active ß-catenin (ABC) and Sox2 population, and this subpopulation was further increased after additional in-vitro radiation treatment, suggesting that radiation resistance of GBM is mediated due, in part, to the activation of stem cell-associated pathways including Wnt. Finally, pharmacological and siRNA inhibition of Wnt pathway significantly decreased the survival and clonogenicity of GBM cells and reduced their ABC(+)/Sox2(+) population. Together, these data suggest that Wnt activation is a molecular mechanism to confer GBM radioresistance and an important therapeutic target.

An empirical evaluation of sampling methods for the classification of imbalanced data.

In numerous classification problems, class distribution is not balanced. For example, positive examples are rare in the fields of disease diagnosis and credit card fraud detection. General machine learning methods are known to be suboptimal for such imbalanced classification. One popular solution is to balance training data by oversampling the underrepresented (or undersampling the overrepresented) classes before applying machine learning algorithms. However, despite its popularity, the effectiveness of sampling has not been rigorously and comprehensively evaluated. This study assessed combinations of seven sampling methods and eight machine learning classifiers (56 varieties in total) using 31 datasets with varying degrees of imbalance. We used the areas under the precision-recall curve (AUPRC) and receiver operating characteristics curve (AUROC) as the performance measures. The AUPRC is known to be more informative for imbalanced classification than the AUROC. We observed that sampling significantly changed the performance of the classifier (paired t-tests P < 0.05) only for few cases (12.2% in AUPRC and 10.0% in AUROC). Surprisingly, sampling was more likely to reduce rather than improve the classification performance. Moreover, the adverse effects of sampling were more pronounced in AUPRC than in AUROC. Among the sampling methods, undersampling performed worse than others. Also, sampling was more effective for improving linear classifiers. Most importantly, we did not need sampling to obtain the optimal classifier for most of the 31 datasets. In addition, we found two interesting examples in which sampling significantly reduced AUPRC while significantly improving AUROC (paired t-tests P < 0.05). In conclusion, the applicability of sampling is limited because it could be ineffective or even harmful. Furthermore, the choice of the performance measure is crucial for decision making. Our results provide valuable insights into the effect and characteristics of sampling for imbalanced classification.

Direct Visualization of UV-Light on Polymer Composite Films Consisting of Light Emitting Organic Micro Rods and Polydimethylsiloxane.

We experimentally demonstrate the direct visualization of ultraviolet (UV) light using flexible polymer composite films consisting of crystalline organic tris-(8-hydroxyquinoline) aluminum (Alq3) micro-rods and polydimethylsiloxane (PDMS). The representative organic mono-molecule Alq3, which is a core material of organic light-emitting diodes, was used to detect light in the invisible UV region and visualize photoluminescence (PL). Alq3 shows absorption in the UV region and light-emitting characteristics in the green region, making it an optimal material for UV visualization because of its large Stokes transition. Crystalline Alq3 micro-rods were fabricated in a deionized water solution through a sequential process of reprecipitation and self-assembly. Highly bright photoluminescence was observed on the highly crystalline Alq3 micro-rods under UV light excitation, indicating that the crystalline structures of Alq3 molecules affect the visible emission decay of excitons. The Alq3 micro-rods were manufactured as flexible polymer composite films using a PDMS solution to observe UV photodetector characteristics according to UV intensity, and it was confirmed that the intensity of the fine UV light reaching the earth's surface can be visualized by making use of this UV photodetector.

Antibody Responses to SARS-CoV-2 in Children With COVID-19.

BACKGROUND: The immunologic features of children with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not clearly delineated. This study was conducted to evaluate SARS-CoV-2-specific antibody responses in children with COVID-19. METHODS: The levels of anti-spike (S) IgG, anti-SARS-CoV-2 IgG, and neutralizing antibody (NAb) were measured during various time points in children <19 years of age with COVID-19 in South Korea from February 2020 to September 2020. RESULTS: One hundred sixty-five blood samples from 114 children with COVID-19 (43.9% asymptomatic and 56.1% mildly symptomatic) were analyzed. In both asymptomatic and mildly symptomatic children, the positive rates of anti-S IgG, anti-SARS-CoV-2 IgG, and NAb were low within 7 days after onset, but they soon reached 100% 14 to <28 days after onset. In symptomatic children, the geometric mean titers (GMTs) of antibodies were all below the positive cutoff during the first 2 weeks from onset and peaked at 28 to <56 days (5.6 for anti-S IgG, 383.6 for anti-SARS-CoV-2 IgG, and 55.0 for NAb, P < .001, respectively). Antibody levels remained detectable up to 3 months after infection. The antibody GMTs during the period 14 to <56 days after symptom onset were highest in children aged 0-4 years. CONCLUSIONS: These results collectively present the humoral immune responses during SARS-CoV-2 infection in children. A further longitudinal study is needed to thoroughly understand the immune system and for effective vaccine development in children during the COVID-19 pandemic.

Population pharmacokinetic analysis of glimepiride with CYP2C9 genetic polymorphism in healthy Korean subjects.

PURPOSE: The purpose of this study was to develop a population pharmacokinetic (PPK) model of glimepiride and to investigate the influence of genetic polymorphisms in CYP2C9 on the PPK of glimepiride in healthy Korean subjects. METHODS: Serum data after a single oral dose of 2 mg of glimepiride in 177 healthy male Korean subjects (CYP2C9*1*1: 163 subjects, *1/*3: 14 subjects) were used. We estimated the PPK of glimepiride using a nonlinear mixed effects modeling (NONMEM) method and explored the possible influence of genetic polymorphisms in CYP2C9 on the PPK of glimepiride. RESULTS: The disposition of glimepiride was best described with a two-compartment model with a Weibull-type absorption and first-order elimination. The visual predictive check indicated that the pharmacokinetic profile of glimepiride was adequately described by the proposed PPK model. The CYP2C9 genotypes as covariate significantly (P < 0.001) influenced the apparent oral clearance (CL/F) of glimepiride. The estimated CL/F of glimepiride was higher (1.60-fold) in CYP2C9*1/*1 subjects than in CYP2C9*1/*3 subjects. CONCLUSIONS: This study indicates that genetic polymorphisms of CYP2C9 influence the substantial interindividual variability in the disposition of glimepiride, and these polymorphisms may affect the clinical response to glimepiride therapy.

Semi-supervised learning for an improved diagnosis of COVID-19 in CT images.

Coronavirus disease 2019 (COVID-19) has been spread out all over the world. Although a real-time reverse-transcription polymerase chain reaction (RT-PCR) test has been used as a primary diagnostic tool for COVID-19, the utility of CT based diagnostic tools have been suggested to improve the diagnostic accuracy and reliability. Herein we propose a semi-supervised deep neural network for an improved detection of COVID-19. The proposed method utilizes CT images in a supervised and unsupervised manner to improve the accuracy and robustness of COVID-19 diagnosis. Both labeled and unlabeled CT images are employed. Labeled CT images are used for supervised leaning. Unlabeled CT images are utilized for unsupervised learning in a way that the feature representations are invariant to perturbations in CT images. To systematically evaluate the proposed method, two COVID-19 CT datasets and three public CT datasets with no COVID-19 CT images are employed. In distinguishing COVID-19 from non-COVID-19 CT images, the proposed method achieves an overall accuracy of 99.83%, sensitivity of 0.9286, specificity of 0.9832, and positive predictive value (PPV) of 0.9192. The results are consistent between the COVID-19 challenge dataset and the public CT datasets. For discriminating between COVID-19 and common pneumonia CT images, the proposed method obtains 97.32% accuracy, 0.9971 sensitivity, 0.9598 specificity, and 0.9326 PPV. Moreover, the comparative experiments with respect to supervised learning and training strategies demonstrate that the proposed method is able to improve the diagnostic accuracy and robustness without exhaustive labeling. The proposed semi-supervised method, exploiting both supervised and unsupervised learning, facilitates an accurate and reliable diagnosis for COVID-19, leading to an improved patient care and management.

Generation of human induced pluripotent stem cell line, KRIBBi003-A, from urinary cells of a patient with glycogen storage disease type IXa.

Glycogen storage disease type IXa (GSD IXa) is a rare genetic disorder characterized by phosphorylase kinase (PhK) deficiency, which leads to excessive glycogen accumulation in the liver. Urinary cells (UCs) were isolated from a GSD IXa patient and reprogrammed into induced pluripotent stem cells (iPSCs) using Sendai virus. The established iPSC line, KRIBBi003-A, exhibited pluripotency marker expression and a normal karyotype. The differentiation capacity of the cell line was confirmed by the differentiation of the three germ layers in vitro. The established iPSC line is a potential useful resource for disease modeling of GSD IXa.

Seroprevalence of scrub typhus, murine typhus and spotted fever groups in North Korean refugees.

OBJECTIVES: The aim of this study was to investigate the seroprevalence of antibodies against scrub typhus, murine typhus and spotted fever groups among North Korean refugees within 1 year of their arrival in South Korea. METHODS: We recruited North Korean refugees who had settled in South Korea after a short stay in a third country and did not have any health problems. The antibody titer was measured using a commercial indirect fluorescence assay immunoglobulin G antibody kit. RESULTS: The seroprevalence of antibodies against scrub typhus, murine typhus, and spotted fever groups among the 99 participants was 22.2%, 17.2%, and 10.1%, respectively, with 8.1% of participants testing positive for both spotted fever and murine typhus. CONCLUSIONS: Refugees may be exposed to rickettsial infections in North Korea and their journey from North Korea. This study is the first to report the seroprevalence of antibodies against the 3 common rickettsial diseases among North Korean refugees. The findings suggest that rickettsial infections should be added to the list of differential diagnoses for North Koreans with fever after entering South Korea.

Comprehensive pharmacogenomic characterization of gastric cancer.

BACKGROUND: Gastric cancer is among the most lethal human malignancies. Previous studies have identified molecular aberrations that constitute dynamic biological networks and genomic complexities of gastric tumors. However, the clinical translation of molecular-guided targeted therapy is hampered by challenges. Notably, solid tumors often harbor multiple genetic alterations, complicating the development of effective treatments. METHODS: To address such challenges, we established a comprehensive dataset of molecularly annotated patient derivatives coupled with pharmacological profiles for 60 targeted agents to explore dynamic pharmacogenomic interactions in gastric cancers. RESULTS: We identified lineage-specific drug sensitivities based on histopathological and molecular subclassification, including substantial sensitivities toward VEGFR and EGFR inhibition therapies in diffuse- and signet ring-type gastric tumors, respectively. We identified potential therapeutic opportunities for WNT pathway inhibitors in ALK-mutant tumors, a significant association between PIK3CA-E542K mutation and AZD5363 response, and transcriptome expression of RNF11 as a potential predictor of response to gefitinib. CONCLUSIONS: Collectively, our results demonstrate the feasibility of drug screening combined with tumor molecular characterization to facilitate personalized therapeutic regimens for gastric tumors.

17-Allylamino-17-demethoxygeldanamycin down-regulates hyaluronic acid-induced glioma invasion by blocking matrix metalloproteinase-9 secretion.

Hyaluronic acid (HA) has been implicated in cell adhesion, motility, and tumor progression in gliomas. We previously reported that HA stimulates secretion of matrix metalloproteinase-9 (MMP-9) and induces glioma invasion. However, the molecular mechanism of HA action and therapeutic strategies for blocking HA-induced MMP-9 secretion remain unknown. Here, we report that the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) blocks MMP-9 secretion and that HA-induced nuclear factor-kappaB (NF-kappaB) activation is mediated by IkappaB kinase, which phosphorylates the NF-kappaB inhibitor IkappaBalpha and promotes its degradation. In addition, using an RNA interference approach, we show that the focal adhesion kinase plays a critical role in mediating HA-induced NF-kappaB activation, which resulted in increased MMP-9 expression and secretion, cell migration, and invasion. Importantly, we show that 17-AAG acts by blocking focal adhesion kinase activation, thereby inhibiting IkappaB kinase-dependent IkappaBalpha phosphorylation/degradation, NF-kappaB activation, and MMP-9 expression. This leads to suppression of HA-induced cell migration and invasion. Based on our data, we propose that 17-AAG is a candidate drug for treatment of highly invasive gliomas resulting from HA-induced, NF-kappaB-mediated MMP-9 secretion.

PIP4K2A as a negative regulator of PI3K in PTEN-deficient glioblastoma.

Glioblastoma (GBM) is the most malignant brain tumor with profound genomic alterations. Tumor suppressor genes regulate multiple signaling networks that restrict cellular proliferation and present barriers to malignant transformation. While bona fide tumor suppressors such as PTEN and TP53 often undergo inactivation due to mutations, there are several genes for which genomic deletion is the primary route for tumor progression. To functionally identify putative tumor suppressors in GBM, we employed in vivo RNAi screening using patient-derived xenograft models. Here, we identified PIP4K2A, whose functional role and clinical relevance remain unexplored in GBM. We discovered that PIP4K2A negatively regulates phosphoinositide 3-kinase (PI3K) signaling via p85/p110 component degradation in PTEN-deficient GBMs and specifically targets p85 for proteasome-mediated degradation. Overexpression of PIP4K2A suppressed cellular and clonogenic growth in vitro and impeded tumor growth in vivo. Our results unravel a novel tumor-suppressive role of PIP4K2A for the first time and support the feasibility of combining oncogenomics with in vivo RNAi screen.

Trend of Daily Sports Participation in Korean Aged Population and Sports Policy: A Review of Research on Public Daily Sports Participation.

BACKGROUND: This study aimed to investigate the trend of physical activity and daily sports participation in the Korean aged population through the review of 'Research on Public Daily Sports Participation' published by the Ministry of Culture, Sports and Tourism. The main purpose was to suggest the best health and sports policy for the future. METHODS: The result of the research conducted by the government was published 13 times in total from 1989 to 2015. The aged were defined as people in their 60s and 70s since 2006. Based on the research published 7 times from 2006 to 2015, this study analyzed the changes and the trend recognition of health status, physical activities, sports activity effects and environment in the aged population in South Korea. RESULTS: Majority of the aged population was found to hardly recognize their health status, but positively aware of physical and sports activity effect, particularly that the sports facility environment has been improving. Therefore, it is encouraged to set up elderly-friendly routine sports environment to motivate their participation and consequently establish healthy exercise culture. CONCLUSION: This study has great significance as it suggests the direction of future health and sports policy by analyzing the trend of previous physical activities and daily sports participation among the aged population based on the government-published research.

Pharmacogenomic landscape of patient-derived tumor cells informs precision oncology therapy.

Outcomes of anticancer therapy vary dramatically among patients due to diverse genetic and molecular backgrounds, highlighting extensive intertumoral heterogeneity. The fundamental tenet of precision oncology defines molecular characterization of tumors to guide optimal patient-tailored therapy. Towards this goal, we have established a compilation of pharmacological landscapes of 462 patient-derived tumor cells (PDCs) across 14 cancer types, together with genomic and transcriptomic profiling in 385 of these tumors. Compared with the traditional long-term cultured cancer cell line models, PDCs recapitulate the molecular properties and biology of the diseases more precisely. Here, we provide insights into dynamic pharmacogenomic associations, including molecular determinants that elicit therapeutic resistance to EGFR inhibitors, and the potential repurposing of ibrutinib (currently used in hematological malignancies) for EGFR-specific therapy in gliomas. Lastly, we present a potential implementation of PDC-derived drug sensitivities for the prediction of clinical response to targeted therapeutics using retrospective clinical studies.

Transforming growth factor-beta1 induces tissue inhibitor of metalloproteinase-1 expression via activation of extracellular signal-regulated kinase and Sp1 in human fibrosarcoma cells.

The net balance of matrix metalloproteinases (MMP) and tissue inhibitor of metalloproteinases (TIMP) system has been known to be a key factor in tumor cell invasion. In the present study, we investigated the molecular mechanisms of anti-invasive and antimigrative activity of transforming growth factor (TGF)-beta1 on HT1080 human fibrosarcoma cells. In in vitro Matrigel invasion and Transwell migration assays, TGF-beta1 dose-dependently inhibited the invasion and migration of HT1080 cells, respectively. Gelatin zymography, Western blot, and real-time PCR analysis showed that TGF-beta1 enhanced the expression and secretion of MMP-2, TIMP-1, and, to a lesser degree, MMP-9 but not membrane type 1-MMP and TIMP-2. The addition of recombinant TIMP-1 protein reduced the Matrigel invasion and Transwell migration of HT1080 cells, similar to TGF-beta1. Because augmentation of TIMP-1 might be the major factor for the anti-invasive and antimigrative activity of TGF-beta1, we investigated possible molecular mechanisms responsible for the expression of TIMP-1 induced by TGF-beta1. Treatment of HT1080 cells with TGF-beta1 rapidly phosphorylated three mitogen-activated protein kinases [MAPK; extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and c-Jun NH2-terminal kinase] and Akt. Among these kinases, the inhibition of only ERK1/2 pathway by PD98059, a specific inhibitor of MAPK/ERK kinase(MEK)-1, and transfection of dominant-negative MEK 1 effectively blocked the TIMP-1 induction by TGF-beta1. Mithramycin, a specific inhibitor of Sp1 transcription factor, but not curcumin, an inhibitor of activator protein-1, and transfection of Sp1 small interfering RNA significantly inhibited the TGF-beta1-induced expression of TIMP-1. In addition, electrophoretic mobility shift assay showed that TGF-beta1 up-regulated Sp1 DNA-binding activity, and PD98059 and mithramycin effectively inhibited these events. Finally, pretreatment of HT1080 cells with PD98059 and mithramycin, but not curcumin, restored the invasive activity of these cells. Taken together, these data suggest that TGF-beta1 modulates the net balance of the MMPs/TIMPs the systems in HT1080 cells for anti-invasion and antimigration by augmenting TIMP-1 through ERK1/2 pathway and Sp1 transcription factor.

Hyaluronic acid induces osteopontin via the phosphatidylinositol 3-kinase/Akt pathway to enhance the motility of human glioma cells.

Hyaluronic acid (HA) binds to cell-surface receptors such as CD44, and seems to be involved in cell adhesion, motility, and tumor progression in brain. To identify gene expression changes that are initiated by HA, we explored human cytokine arrays in U87MG glioma cells and identified osteopontin, a secreted matrix protein, as a transcriptional target of HA. Interestingly, expression of osteopontin was induced by HA in glioma cells lacking functional PTEN, a tumor suppressor gene (U87MG, U251MG, and U373MG), but not in wild-type (wt)-PTEN-harboring cells (LN18 and LN428). To confirm the role of PTEN, adenoviral (Ad)-wt-PTEN was used to induce ectopic expression of wt-PTEN in U87MG cells, leading to reduced HA-mediated osteopontin induction. Reciprocally, transfection with dominant-negative Akt repressed HA-induced osteopontin expression. Furthermore, HA promoted the motility of glioma cells, and down-regulation of induced osteopontin activity via a neutralizing anti-osteopontin antibody repressed HA-induced motility in vitro. Together, these results strongly suggest that induction of osteopontin expression by HA is dependent on activation of the phosphatidylinositol 3-kinase/Akt pathway. Furthermore, our data indicate that PTEN can effectively modulate the expression of osteopontin, and HA-induced osteopontin plays an important role in the motility response induced by HA in human glioma cells.