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OPN Expression (opn + expression)
Selected AbstractsIncreased osteopontin expression following intranigral lipopolysaccharide injection in the ratEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2005Joanna Iczkiewicz Abstract Nigral cell death in Parkinson's disease is characterized by glial cell activation leading to inflammatory changes. Osteopontin (OPN) is a glycosylated phosphoprotein that is induced by inflammatory mediators and which we have previously shown to be present in the substantia nigra. However, the role of OPN in the nigral inflammation is not known. We now report on the effects of lipopolysaccharide (LPS)-induced glial cell activation in the substantia nigra of rats on OPN expression. LPS administration induced dopaminergic cell death as shown by reduced nigral tyrosine hydroxylase immunoreactivity. There was a corresponding time-dependent increase in both OPN mRNA, which was maximal at 48 h, and protein levels, which peaked at 72 h before returning to control levels by 120 h. This increase was accompanied by marked reactive gliosis as shown by increased OX-42, glial fibrillary acidic protein (GFAP) and ED1 immunoreactivity. OX-42-positive cells increased in a time-dependent manner, peaking at 72 h before returning to control levels at 120 h. Similarly, ED1-positive cells were present in their greatest numbers at 24 h but then gradually declined. These changes mirrored the alterations occurring in OPN protein and OPN mRNA, respectively. In contrast, GFAP-positive cells only started to increase in number at 120 h. Colocalization studies showed that OPN was present in both ED1- and OX-42-positive cells but not in GFAP-positive cells. These data confirm that intranigral injection of LPS induces a rapid and marked gliosis that accompanies the loss of tyrosine hydroxylase-positive neurones and suggest that, after glial cell activation, enhanced expression of OPN occurs linked to increased numbers of microglia and/or macrophages. This suggests that OPN may be functionally important in the control of inflammatory changes. [source] Osteopontin and the skin: multiple emerging roles in cutaneous biology and pathologyEXPERIMENTAL DERMATOLOGY, Issue 9 2009Franziska Buback Abstract:, Osteopontin (OPN) is a glycoprotein expressed by various tissues and cells. The existence of variant forms of OPN as a secreted (sOPN) and intracellular (iOPN) protein and its modification through post-translational modification and proteolytic cleavage explain its broad range of functions. There is increasing knowledge which receptors OPN isoforms can bind to and which signaling pathways are activated to mediate different OPN functions. sOPN interacts with integrins and CD44, mediates cell adhesion, migration and tumor invasion, and has T helper 1 (Th1) cytokine functions and anti-apoptotic effects. iOPN has been described to regulate macrophage migration and interferon-, secretion in plasmacytoid dendritic cells. Both sOPN and iOPN, through complex functions for different dendritic cell subsets, participate in the regulation of Th cell lineages, among them Th17 cells. For skin disease, OPN from immune cells and tumor cells is of pathophysiological relevance. OPN is secreted in autoimmune diseases such as lupus erythematosus, and influences inflammation of immediate and delayed type allergies and granuloma formation. We describe that OPN is overexpressed in psoriasis and propose a model to study OPN function in psoriatic inflammation. Through cytokine functions, OPN supports immune responses against Mycobacteria and viruses such as herpes simplex virus. OPN is also implicated in skin tumor progression. Overexpression of OPN influences invasion and metastasis of melanoma and squamous cell carcinoma cells, and OPN expression in melanoma is a possible prognostic marker. As OPN protein preparations and anti-OPN antibodies may be available in the near future, in-depth knowledge of OPN functions may open new therapeutic approaches for skin diseases. [source] Clinical significance of osteopontin expression in T1 and T2 tongue cancersHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 6 2008Chih-Yen Chien MD Abstract Background Osteopontin (OPN) is considered to be a tumor-related protein associated with tumor aggressiveness and metastasis. Methods Immunohistochemistry was used to study the clinical significance of OPN expression in T1 and T2 tongue cancers. Results Positive OPN expression significantly correlated with higher tumor classification (T) (p = .004), positive nodal classification (N) (p < .001), greater tumor thickness (p < .001), and presence of tumor necrosis (p = .016), respectively. The unfavorable cumulative 5-year disease-free survival rate significantly correlated with positive OPN expression (p < .001), T2 (p = .024), positive N (p < .001), greater tumor thickness (p = .023), and positive tumor necrosis (p = .003). However, taking CD105 into consideration, only CD105 expression was the independent prognostic factor for survival by Cox's regression analysis. Conclusion Overexpression of OPN in the tumors implicated a more aggressive tumor behavior and was an important factor for survival. In addition, there might be relationship between OPN and CD105 expressions in angiogenesis. © 2008 Wiley Periodicals, Inc. Head Neck, 2008 [source] Thirty-kilodalton Tat-interacting protein suppresses tumor metastasis by inhibition of osteopontin transcription in human hepatocellular carcinoma,HEPATOLOGY, Issue 1 2008Jian Zhao It has been previously demonstrated that the 30-kDa Tat-interacting protein (TIP30) plays an important role in the suppression of hepatocarcinogenesis by acting as a tumor suppressor. Here we report that TIP30 suppresses metastasis of hepatocellular carcinoma (HCC) through inhibiting the transcription of osteopontin (OPN), a key molecule in the development of tumor metastasis. The expression of TIP30 messenger RNA was reverse to that of OPN messenger RNA in HCC cell lines. Ectopic expression of TIP30 greatly suppressed OPN expression, inhibited invasion of HCC cells through extracellular matrix (ECM) and adhesion with fibronectin in vitro, whereas down-regulation of TIP30 by RNA-mediated interference enhanced OPN expression and promoted metastatic abilities of HCC cells in vitro. Moreover, overexpression of TIP30 significantly inhibited the growth and lung metastases of HCC cells in nude mice. In contrast, down-regulation of TIP30 greatly promoted tumor cell growth and metastases in vivo. TIP30 repressed OPN transcription through interaction with Ets-1 and suppressed the transcriptional activity of Ets-1 and synergistic actions of Ets-1 and alkaline phosphatase-1. Thus, TIP30 may act as an Ets-1 modulator and inhibit tumor metastasis through abrogating Ets-1,dependent transcription. Moreover, expression of TIP30 was inversely associated with OPN expression in HCC tissue samples as detected by immunohistochemistry assay. Conclusion: Our results reveal a novel pathway by which OPN and possibly other Ets-1 target genes involved in tumor metastasis are regulated by TIP30 and elucidate a mechanism for metastasis promoted by TIP30 deficiency. (HEPATOLOGY 2008.) [source] Role of osteopontin in neutrophil functionIMMUNOLOGY, Issue 4 2007Adeline Koh Summary Osteopontin (OPN) is important for the function of fibroblasts, macrophages and lymphocytes during inflammation and wound healing. In recent studies of experimental colitis we demonstrated exacerbated tissue destruction in OPN-null mice, associated with reduced tumour necrosis factor-, expression and increased myeloperoxidase activity. The objective of this investigation therefore was to determine the importance of OPN expression in neutrophil function. Although, in contrast to macrophages, neutrophils expressed low levels of OPN with little or no association with the CD44 receptor, intraperitoneal recruitment of neutrophils in OPN-null mice was impaired in response to sodium periodate. The importance of exogenous OPN for neutrophil recruitment was demonstrated by a robust increase in peritoneal infiltration of PMNs in response to injections of native or recombinant OPN. In vitro, OPN,/, neutrophils exhibited reduced chemokinesis and chemotaxis towards N -formyl methionyl leucyl phenylalanine (fMLP), reflecting a reduction in migration speed and polarization. Exogenous OPN, which was chemotactic for the neutrophils, rescued the defects in polarization and migration speed of the OPN,/, neutrophils. In contrast, the defensive and cytocidal activities of OPN,/, neutrophils, measured by assays for phagocytosis, generation of reactive oxygen species, cytokine production and matrix metalloproteinase-9, were not impaired. These studies demonstrate that, while exogenous OPN may be important for the recruitment and migration of neutrophils, expression of OPN by neutrophils is not required for their destructive capabilities. [source] Gene expression profiling during rat mammary carcinogenesis induced by 7,12-dimethylbenz[a]anthraceneINTERNATIONAL JOURNAL OF CANCER, Issue 6 2009Masakazu Souda Abstract 7,12-Dimethylbenz[a]anthracene (DMBA)-induced rat mammary carcinoma is a well-recognized model; however, the genetic alterations during its carcinogenesis have yet to be determined. We used laser capture microdissection to specifically isolate cells from terminal end buds (TEBs), the origin of carcinoma, at 2 weeks after sesame oil treatment (control) or DMBA treatment (DMBA-TEBs), ductal carcinoma in situ (DCIS) and invasive mammary carcinoma (MC). Using an oligonucleotide microarray representing 20,600 rat probe sequences, we analyzed gene expression profiles and validated mRNA and protein levels of genes of interest byreal-time quantitative PCR and immunohistochemistry. The number of differentially expressed genes dramatically increased from DMBA-TEBs (63) to DCIS (798) and MC (981). Only the expression of PEP-19, an anti-apoptotic gene, showed significant increases in DMBA-TEBs (4-fold), DCIS (10-fold) and MC (16-fold). MMP-13 expression was increased markedly in DCIS (19-fold) and MC (61-fold) while OPN expression was increased 6-fold in DCIS and 8-fold in MC. MMP-7 expression was increased 4-fold in MC. Nidogen-1; a participant in the assembly of basement membranes, TSP-2; an inhibitor of angiogenesis and COUP-TFI; a transcription repressor showed significant decreases in DCIS (4-, 9- and 17-fold, respectively) and MC (10-, 37- and 100-fold). Network analyses with IPA software revealed that the most significant network included Akt groups in DCIS and ERK groups in MC. The present findings provide us with a better understanding of the molecular alteration that occur during mammary carcinogenesis and suggest the importance of PEP-19 overexpression in the very early stage of mammary carcinogenesis. © 2009 UICC [source] Downregulation of osteopontin contributes to metastasis suppression by breast cancer metastasis suppressor 1INTERNATIONAL JOURNAL OF CANCER, Issue 3 2008Benjamin D. Hedley Abstract Breast cancer metastasis suppressor 1 (BRMS1) inhibits the ability of multiple human and murine cancer cell lines to metastasize to lymph nodes, bones and lungs. Comparison of mRNA expression in metastatic MDA-MB-435 human carcinoma cells (435) and metastasis-suppressed BRMS1 transfectants (435/BRMS1) showed a marked (>90%) reduction of osteopontin (OPN) mRNA and protein expression in BRMS1-overexpressing cells. OPN expression is associated with disease progression in patients, with higher levels of OPN produced by cancer cells associated with poorer patient survival. Furthermore, OPN has been suggested to promote survival of cancer cells in response to stress, although the mechanisms by which this may occur remain poorly understood. This study tested the hypothesis that re-expression of OPN in metastasis-suppressed 435/BRMS1 cells would reverse metastasis suppression and confer protection from stress-induced apoptosis. A stable pooled population of OPN overexpressing 435/BRMS1 cells was created (435/BRMS1/OPN). OPN re-expression did not affect in vitro cell growth rates; however, increased anchorage independent growth/survival and protection from hypoxia-induced apoptosis was observed (p < 0.05). In vivo, OPN re-expression in BRMS1 transfected cells did not affect in vivo primary tumor growth but did increase the incidence of spontaneous metastasis to lymph nodes and lungs in mice. These novel findings suggest that OPN downregulation by BRMS1 may be responsible, at least in part, for BRMS1-mediated metastasis suppression by sensitizing cancer cells to stress induced apoptosis. These studies clarify one mechanism by which BRMS1 can suppress metastasis. © 2008 Wiley-Liss, Inc. [source] Upregulation of Osteopontin by Osteocytes Deprived of Mechanical Loading or Oxygen,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2005Ted S Gross PhD Abstract The pathway(s) by which disuse is transduced into locally mediated osteoclastic resorption remain unknown. We found that both acute disuse (in vivo) and direct hypoxia (in vitro) induced rapid upregulation of OPN expression by osteocytes. Within the context of OPN's role in osteoclast migration and attachment, hypoxia-induced osteocyte OPN expression may serve to mediate disuse-induced bone resorption. Introduction: We have recently reported that disuse induces osteocyte hypoxia. Because hypoxia upregulates osteopontin (OPN) in nonconnective tissue cells, we hypothesized that both disuse and hypoxia would rapidly elevate expression of OPN by osteocytes. Materials and Methods: The response of osteocytes to 24 h of disuse was explored by isolating the left ulna diaphysis of adult male turkeys from loading (n = 5). Cortical osteocytes staining positive for OPN were determined using immunohistochemistry and confocal microscopy. In vitro experiments were performed to determine if OPN expression was altered in MLO-Y4 osteocytes by direct hypoxia (3, 6, 24, and 48 h) or hypoxia (3 and 24 h) followed by 24 h of reoxygenation. A final in vitro experiment explored the potential of protein kinase C (PKC) to regulate hypoxia-induced osteocyte OPN mRNA alterations. Results: We found that 24 h of disuse significantly elevated osteocyte OPN expression in vivo (145% versus intact bones; p = 0.02). We confirmed this finding in vitro, by observing rapid and significant upregulation of OPN protein expression after 24 and 48 h of hypoxia. Whereas 24 h of reoxygenation after 3 h of hypoxia restored normal osteocyte OPN expression levels, 24 h of reoxygenation after 24 h of hypoxia did not mitigate elevated osteocyte OPN expression. Finally, preliminary inhibitor studies suggested that PKC serves as a potent upstream regulator of hypoxia-induced osteocyte OPN expression. Conclusions: Given the documented roles of OPN as a mediator of environmental stress (e.g., hypoxia), an osteoclast chemotaxant, and a modulator of osteoclastic attachment to bone, we speculate that hypoxia-induced osteocyte OPN expression may serve to mediate disuse-induced osteoclastic resorption. Furthermore, it seems that a brief window of time exists in which reoxygenation (as might be achieved by reloading bone) can serve to inhibit this pathway. [source] Osteopontin expression correlates with prognostic variables and survival in clear cell renal cell carcinomaJOURNAL OF SURGICAL ONCOLOGY, Issue 4 2006Koviljka Matusan MD Abstract Background and Objectives Osteopontin (OPN) is a phosphorylated glycoprotein with diverse functions including tumorigenesis and tumor cell metastasis. Recently, it has been detected in a growing number of human tumors, and assessed as a potential prognostic marker. The aim of this study was to analyze the expression of OPN in normal renal tissue and clear cell renal cell carcinomas (CRCCs), and to assess its prognostic significance. Methods The expression of OPN protein was immunohistochemically analyzed in 171 CRCCs and compared to usual clinicopathological parameters such as tumor size, nuclear grade, pathological stage, Ki-67 proliferation index, and cancer-specific survival. Results In normal renal parenchyma, the expression of OPN was seen in distal tubular epithelial cells, calcifications, and some stromal cells. The upregulation of OPN was observed in 61 CRCCs (35.7%) in the form of cytoplasmic granular staining of various intensities. Statistical analysis showed correlation of the OPN expression with tumor size (P,<,0.001), Fuhrman nuclear grade (P,<,0.001), pathological stage (P,=,0.011), and Ki-67 proliferation index (P,<,0.001). Moreover, patients with OPN-positive tumors had significantly worse prognosis in comparison to patients with tumors lacking OPN protein (P,=,0.004). Conclusion Our results suggest that overexpression of OPN is involved in the progression of CRCC. J. Surg. Oncol. 2006;94:325,331. © 2006 Wiley-Liss, Inc. [source] Osteopontin is expressed and functional in human eosinophilsALLERGY, Issue 2 2010I. Puxeddu To cite this article: Puxeddu I, Berkman N, Ribatti D, Bader R, Haitchi HM, Davies DE, Howarth PH, Levi-Schaffer F. Osteopontin is expressed and functional in human eosinophils. Allergy 2010; 65: 168,174. Abstract Background:, Eosinophils are critically involved in allergic inflammation and tissue remodeling. Osteopontin (OPN) is a glycoprotein molecule which exhibits pro-fibrogenic and pro-angiogenic properties and has recently also been implicated in allergic diseases. In this study, we investigated the expression and function of OPN in human eosinophils. Methods:, Osteopontin mRNA (RT-PCR) and protein (immunofluorescence) expression in peripheral blood eosinophils from atopic human subjects were evaluated. Soluble OPN release was determined in resting and activated eosinophils. The contribution of OPN to eosinophil-induced angiogenesis was determined using the chick embryo chorio- allantoic membrane (CAM) assay and OPN-induced eosinophil chemotaxis was determined (ChemoTx System microplate wells). Finally, OPN expression in bronchoalveolar lavage (BAL) fluids from mild asthmatic and normal control subjects was determined. Results:, Osteopontin is expressed in human eosinophils and is increased following GM-CSF and IL-5 activation. Eosinophil-derived OPN contributes to eosinophil-induced angiogenesis. Recombinant OPN promotes eosinophil chemotaxis in vitro and this effect is mediated by ,4,1 integrin binding. Soluble OPN is increased in the bronchoalveolar lavage fluid from mild asthmatic subjects and correlates with eosinophil counts. Conclusions:, We therefore conclude that OPN is likely to contribute to the process of angiogenesis observed in the airways in asthma. [source] Expression of osteopontin in chronic rhinosinusitis with and without nasal polypsALLERGY, Issue 1 2009X. Lu Background:, Osteopontin (OPN) is a multifunctional 34-kDa extracellular matrix protein that can influence the inflammatory process. However, the presence of OPN in human sinonasal mucosa and its roles in the inflammatory process of chronic rhinosinusitis (CRS) are not clear. This study investigated the expression of OPN in human sinonasal mucosa, its cytokine-driven expression regulation, and its effect on cytokine production in sinonasal mucosa. Methods:, Surgical samples were investigated by means of quantitative reverse transcriptase polymerase chain reaction for evaluation of OPN messenger RNA (mRNA) expression, and the presence and location of OPN protein expression were analyzed using immunohistochemistry. Furthermore, nasal explant culture was used to investigate the mutual regulatory interactions between interferon (IFN)-,, interleukin (IL)-4, IL-5, IL-13, IL-1,, and tumor necrosis factor (TNF)-, and OPN in sinonasal mucosa. Results:, Osteopontin expression was significantly upregulated in CRS tissues compared with control tissues. There was a further significant increase of OPN expression in patients with nasal polyps (NPs) and asthma. Immunohistochemistry revealed positive staining of OPN in epithelial cells, submucosal glands, infiltrating cells, and extracellular matrix. Osteopontin mRNA was induced by IFN-,, IL-1,, and TNF-,, but inhibited by IL-4 and IL-13. On the contrary, OPN induced IFN-,, IL-4, IL-5, IL-13, IL-1,, and TNF-, production in sinonasal mucosa. Conclusions:, The expression of OPN is upregulated in CRS. The mutual regulatory interactions between OPN and inflammatory cytokines suggest that OPN may play an important role in the pathogenesis of CRS. [source] The functional ,443T/C osteopontin promoter polymorphism influences osteopontin gene expression in melanoma cells via binding of c-Myb transcription factorMOLECULAR CARCINOGENESIS, Issue 1 2009Julia Schultz Abstract In the present report, the possible role of a recently described functional polymorphism of the osteopontin (OPN) promoter at position ,443 (,443T/C) for OPN expression in melanoma cells was addressed. As shown by real-time PCR analysis, melanoma metastases that were homozygous for the ,443C allele expressed significantly higher levels of OPN mRNA compared with those that were either heterozygous (,443T/C) or homozygous for the ,443T allele. In line with this, immunoblotting showed significantly enhanced baseline and bFGF-induced OPN protein expression in melanoma cell lines which were homozygous for the ,443C allele, compared with cell lines with other allelic variants. Similar results were obtained in in vitro luciferase assays. Chromatin immunoprecipitation (ChIP) demonstrated binding of c-Myb to the ,443 OPN promoter region, and binding could significantly be enhanced after bFGF stimulation. Moreover, as shown by electrophoretic mobility shift assays (EMSA), recombinant DNA-binding domain of c-Myb bound in a sequence-specific manner to this region. Finally, the role of c-Myb for OPN gene regulation via binding to the ,443 promoter region could be further substantiated by ectopic overexpression of c-Myb in melanoma cells, using different reporter gene constructs. Taken together, it is demonstrated that the ,443 promoter region exerts influence on OPN gene expression in melanoma cells, and differential binding of c-Myb transcription factor appears to play a major role in this process. These findings might be a feasible explanation for different OPN expression levels in metastatic tumors and may also have prognostic and therapeutic relevance. © 2008 Wiley-Liss, Inc. [source] Osteopontin stimulates invasion of NCI-h295 cells but is not associated with survival in adrenocortical carcinoma,THE JOURNAL OF PATHOLOGY, Issue 2 2009Dirk Weismann Abstract Gene array studies indicated that osteopontin (OPN) mRNA is highly expressed in adrenocortical carcinomas (ACCs). OPN enhances invasiveness, proliferation, and metastasis formation, and is associated with poor survival in some malignant diseases. Integrin ,v,3 has been shown to mediate OPN effects on invasion. In this study, we demonstrated OPN and integrin ,v,3 expression in normal adrenal glands and benign adenomas, with staining seen exclusively in adrenocortical cells as well as even stronger staining in ACC. Western blot analysis confirmed overexpression of OPN in ACC (p < 0.01). With Matrigel invasion assays, we have shown that OPN greatly stimulates the invasiveness of NCI-h295 cells (>six-fold increase, p < 0.001). Transfection with integrin ,v,3 further increased invasiveness after OPN stimulation (p < 0.001). This increase was reversed by the addition of an anti-integrin ,3 antibody, indicating a functional relationship of OPN and integrin ,v,3 in ACC. With tissue arrays, we confirmed high OPN expression in 147 ACC samples. However, no association with survival was seen in Kaplan-Meier analysis including 111 patients with primary tumours graded for OPN staining and follow-up data available. In conclusion, our in vitro data indicate that OPN and integrin ,v,3 may act as a functional complex facilitating the invasiveness of adrenocortical tumours. This relationship remains of relevance to our understanding of carcinogenesis, but further studies are needed to address the physiological and pathological function of OPN in adrenal tissue. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Specifically modified osteopontin in rheumatoid arthritis fibroblast-like synoviocytes supports interaction with B cells and enhances production of interleukin-6ARTHRITIS & RHEUMATISM, Issue 12 2009Yasuhiro Take Objective Osteopontin (OPN) is expressed by fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA), but its pathologic role is still obscure. The present study was undertaken to analyze the role of OPN in RA by focusing on its effects on cell,cell interactions between FLS and B lymphocytes. Methods FLS obtained from 10 patients with RA and 10 non-RA subjects and a B lymphocyte cell line were studied. The characteristics of OPN expression by FLS were analyzed by Western blotting, immunoprecipitation, and immunofluorescence studies. In cocultures of FLS and B lymphocytes, the effects of OPN on adhesion of B lymphocytes to FLS and the consequent production of interleukin-6 (IL-6) were analyzed in experiments involving overexpression and knockdown of OPN and inhibitory studies with an OPN-blocking antibody. In vivo, the expression of OPN in RA synovium was examined by immunohistochemistry. Results A specifically modified 75-kd form of OPN was predominantly expressed in RA FLS, and this was associated with expression of >200-kd thrombin-cleaved OPN that was crosslinked with fibronectin and localized on the surface of the FLS. In FLS,B lymphocyte cocultures, 75-kd OPN,positive FLS produced a significantly higher amount of IL-6 than did 75-kd OPN,negative FLS. When the FLS were separated from B lymphocytes or cultured alone, the production of IL-6 was low and was not significantly different between these 2 culture conditions. Moreover, OPN overexpression enhanced production of IL-6 in 75-kd OPN,positive FLS,B lymphocyte cocultures. Addition of the OPN-blocking antibody inhibited the adhesion of B lymphocytes to FLS. Immunohistochemical analyses revealed that localization of IL-6,positive cells coincided with the sites at which OPN and B lymphocytes were colocalized. Conclusion Specifically modified 75-kd OPN was expressed by RA FLS. This form of OPN affected FLS,B lymphocyte interactions by supporting the adhesion of B lymphocytes to FLS and enhancing the production of IL-6. [source] | ||||||||||