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PloS One 2015Osteopontin (OPN) plays an important role in many physiological and pathological processes (wound healing, inflammation, immune response, and tumorigenesis). This... (Meta-Analysis)
Meta-Analysis Review
AIMS
Osteopontin (OPN) plays an important role in many physiological and pathological processes (wound healing, inflammation, immune response, and tumorigenesis). This meta-analysis assessed the diagnostic value of osteopontin in ovarian cancer.
METHODS AND RESULTS
Searches in Embase and PubMed were conducted, in order to identify eligible studies on osteopontin expression and its diagnostic value in ovarian cancer. The revised Quality Assessment for Studies of Diagnostic Accuracy (QUADAS-2) tool was applied to examine the quality of these studies and the overall osteopontin diagnostic accuracy in ovarian cancer was pooled using the bivariate model. The publication bias was assessed using funnel plots and Deek's test. This search methodology resulted in 13 studies with a total of 839 ovarian cancer patients and 1439 controls in this meta-analysis. The overall osteopontin diagnostic sensitivity and specificity of ovarian cancer were 0.66 (95% CI, 0.51-0.78) and 0.88 (95% CI, 0.78-0.93), respectively. The area under summary receiver operating characteristic (sROC) curves (AUC) was 0.85 (95%CI, 0.81-0.88). There was no significant publication bias observed across the eligible studies. However, a major design deficiency of the eligible studies is the issue of subject selection bias.
CONCLUSIONS
Osteopontin could be a useful biomarker in diagnosis of ovarian cancer. Due to the design deficits of the eligible studies, a future study with a larger sample size and better design is needed to rigorously confirm the diagnostic potential of osteopontin in ovarian cancer.
Topics: Female; Humans; Osteopontin; Ovarian Neoplasms
PubMed: 25951060
DOI: 10.1371/journal.pone.0126444 -
Matrix Biology : Journal of the... Jul 2014Osteopontin (OPN) is a multifunctional cytokine that impacts cell proliferation, survival, drug resistance, invasion, and stem like behavior. Due to its critical... (Review)
Review
Osteopontin (OPN) is a multifunctional cytokine that impacts cell proliferation, survival, drug resistance, invasion, and stem like behavior. Due to its critical involvement in regulating cellular functions, its aberrant expression and/or splicing is functionally responsible for undesirable alterations in disease pathologies, specifically cancer. It is implicated in promoting invasive and metastatic progression of many carcinomas. Due to its autocrine and paracrine activities OPN has been shown to be a crucial mediator of cellular cross talk and an influential factor in the tumor microenvironment. OPN has been implicated as a prognostic and diagnostic marker for several cancer types. It has also been explored as a possible target for treatment. In this article we hope to provide a broad perspective on the importance of OPN in the pathophysiology of cancer.
Topics: ATP Binding Cassette Transporter, Subfamily B; Biomarkers, Tumor; Disease Progression; Drug Delivery Systems; Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Osteopontin; Signal Transduction
PubMed: 24657887
DOI: 10.1016/j.matbio.2014.03.001 -
Journal of Thrombosis and Haemostasis :... May 2022Osteopontin (OPN) is a multifunctional proinflammatory matricellular protein overexpressed in multiple human cancers and associated with tumor progression and...
BACKGROUND
Osteopontin (OPN) is a multifunctional proinflammatory matricellular protein overexpressed in multiple human cancers and associated with tumor progression and metastases. Thrombin cleavage of OPN reveals a cryptic binding site for α β and α β integrins.
METHODS
Thrombin cleavage-resistant OPN knock-in (OPN-KI) mice were generated and compared to OPN deficient mice (OPN-KO) and wild type (WT) mice in their ability to support growth of melanoma cells. Flow cytometry was used to analyze tumor infiltrating leukocytes.
RESULTS
OPN-KI mice engineered with a thrombin cleavage-resistant OPN had reduced B16 melanoma growth and fewer pulmonary metastases than WT mice. The tumor suppression phenotype of the OPN-KI mouse was identical to that observed in OPN-KO mice and was replicated in WT mice by pharmacologic inhibition of thrombin with dabigatran. Tumors isolated from OPN-KI mice had increased tumor-associated macrophages with an altered activation phenotype. Immunodeficient OPN-KI mice (NOG-OPN-KI) or macrophage-depleted OPN-KI mice did not exhibit the tumor suppression phenotype. As B16 cells do not express OPN, thrombin-cleaved fragments of host OPN suppress host antitumor immune response by functionally modulating the tumor-associated macrophages. YUMM3.1 cells, which express OPN, showed less tumor suppression in the OPN-KI and OPN-KO mice than B16 cells, but its growth was suppressed by dabigatran similar to B16 cells.
CONCLUSIONS
Thrombin cleavage of OPN, derived from the host and the tumor, initiates OPN's tumor-promoting activity in vivo.
Topics: Animals; Cell Adhesion; Dabigatran; Humans; Melanoma, Experimental; Mice; Osteopontin; Thrombin
PubMed: 35108449
DOI: 10.1111/jth.15663 -
Mediators of Inflammation 2017Complex interactions between tumor and host cells regulate systemic tumor dissemination, a process that begins early at the primary tumor site and goes on until tumor... (Review)
Review
Complex interactions between tumor and host cells regulate systemic tumor dissemination, a process that begins early at the primary tumor site and goes on until tumor cells detach themselves from the tumor mass and start migrating into the blood or lymphatic vessels. Metastatic cells colonize the target organs and are capable of surviving and growing at distant sites. In this context, osteopontin (OPN) appears to be a key determinant of the crosstalk between cancer cells and the host microenvironment, which in turn modulates immune evasion. OPN is overexpressed in several human carcinomas and has been implicated in inflammation, tumor progression, and metastasis. Thus, it represents one of the most attracting targets for cancer therapy. Within the tumor mass, OPN is secreted in various forms either by the tumor itself or by stroma cells, and it can exert either pro- or antitumorigenic effects according to the cell type and tumor microenvironment. Thus, targeting OPN for therapeutic purposes needs to take into account the heterogeneous functions of the multiple OPN forms with regard to cancer formation and progression. In this review, we will describe the role of systemic, tumor-derived, and stroma-derived OPN, highlighting its pivotal role at the crossroads of inflammation and tumor progression.
Topics: Animals; Disease Progression; Humans; Inflammation; Neoplasm Metastasis; Osteopontin
PubMed: 28769537
DOI: 10.1155/2017/4049098 -
The Journal of Infectious Diseases Jul 2023People with human immunodeficiency virus (HIV) have heightened incidence/risk of diastolic dysfunction and heart failure. Women with HIV have elevated cardiac fibrosis,...
BACKGROUND
People with human immunodeficiency virus (HIV) have heightened incidence/risk of diastolic dysfunction and heart failure. Women with HIV have elevated cardiac fibrosis, and plasma osteopontin (Opn) is correlated to cardiac pathology. Therefore, this study provides mechanistic insight into the relationship between osteopontin and cardiac fibrosis during HIV infection.
METHODS
Mouse embryonic fibroblasts (MEFs) modeled cardiac fibroblasts in vitro. Simian immunodeficiency virus (SIV)-infected macaques with or without antiretroviral therapy and HIV-infected humanized mice modeled HIV-associated cardiac fibrosis.
RESULTS
Lipopolysaccharide-stimulated MEFs were myofibroblast-like, secreted cytokines, and produced Opn transcripts. SIV-infected animals had elevated plasma Opn at necropsy, full-length Opn in the ventricle, and ventricular interstitial fibrosis. Regression modeling identified growth differentiation factor 15, CD14+CD16+ monocytes, and CD163 expression on CD14+CD16+ monocytes as independent predictors of plasma Opn during SIV infection. HIV-infected humanized mice showed increased interstitial fibrosis compared to uninfected/untreated animals, and systemic inhibition of osteopontin by RNA aptamer reduced left ventricle fibrosis in HIV-infected humanized mice.
CONCLUSIONS
Since Opn is elevated in the plasma and left ventricle during SIV infection and systemic inhibition of Opn reduced cardiac fibrosis in HIV-infected mice, Opn may be a potential target for adjunctive therapies to reduce cardiac fibrosis in people with HIV.
Topics: Humans; Animals; Female; Mice; HIV Infections; Osteopontin; Fibroblasts; Heart; Cardiomyopathies; Simian Immunodeficiency Virus; Fibrosis; Macaca; HIV; Simian Acquired Immunodeficiency Syndrome
PubMed: 37162508
DOI: 10.1093/infdis/jiad149 -
Alzheimer's & Dementia : the Journal of... Jan 2024The secreted phosphoprotein 1 (SPP1) gene expressed by CD11c cells is known to be associated with microglia activation and neuroinflammatory diseases. As most studies...
INTRODUCTION
The secreted phosphoprotein 1 (SPP1) gene expressed by CD11c cells is known to be associated with microglia activation and neuroinflammatory diseases. As most studies rely on mouse models, we investigated these genes and proteins in the cortical brain tissue of older adults and their role in Alzheimer's disease (AD) and related disorders.
METHODS
We leveraged protein measurements, single-nuclei, and RNASeq data from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP) of over 1200 samples for association analysis.
RESULTS
Expression of SPP1 and its encoded protein osteopontin were associated with faster cognitive decline and greater odds of common neuropathologies. At single-cell resolution, integrin subunit alpha X (ITGAX) was highly expressed in microglia, where specific subpopulations were associated with AD and cerebral amyloid angiopathy.
DISCUSSION
The study provides evidence of SPP1 and ITGAX association with cognitive decline and common neuropathologies identifying a microglial subset associated with disease.
Topics: Animals; Mice; Alzheimer Disease; Cerebral Amyloid Angiopathy; Cognition; Cognitive Dysfunction; Osteopontin
PubMed: 37727065
DOI: 10.1002/alz.13474 -
Journal of Advanced Research Nov 2022Cigarette smoking is the main risk factor for lung cancer. MSCs in the TME promoting tumor angiogenesis, growth, and metastasis. SIBLING proteins enable cancer cells to...
INTRODUCTION
Cigarette smoking is the main risk factor for lung cancer. MSCs in the TME promoting tumor angiogenesis, growth, and metastasis. SIBLING proteins enable cancer cells to extend, invade and metastasize.
OBJECTIVES
Cigarette smoke promotes the progression and metastasis of lung cancer, although how this occurs is poorly understood. We evaluated the impact of whether cigarette smoking motivates SIBLING protein expression and is involved in MSC-mediated lung tumor metastasis.
METHODS
We investigated the expression of OPN in the Gene Expression Omnibus (GEO) databases and confirmed the results by immunohistochemistry (IHC), qPCR and Western blotting (WB) of lung cancer cells and tissues. The effect of OPN on the recruitment and adhesion of mesenchymal stem cells (MSCs) to lung cancer cells and lung cancers metastasis was investigated by Transwell, adhesion assays. A series of in vitro and in vivo experiments were conducted to demonstrate the mechanisms by which OPN modulates recruitment and adhesion of MSCs to lung cancer cells and lung cancer metastasis.
RESULTS
Cigarette smoke extract (CSE) and benzo[α]pyrene (B[α]P) increased levels of OPN expression and facilitated the recruitment and adhesion of MSCs to lung cancer cells via JAK2/STAT3 signaling. We also observed that OPN promotes tumor-associated MSC (TA-MSC) formation through the OPN receptor (integrins αvβ1, αvβ3, αvβ5 or CD44), inducing lung cancer cell migration and invasion. In an orthotopic mouse model of lung cancer, increases in OPN expression promoted by cigarette smoke upregulated MSC recruitment and facilitated lung cancer metastasis. Knockdown of OPN expression inhibited cigarette smoke-induced lung cancer metastasis in vivo.
CONCLUSION
Cigarette smoke increases OPN expression through the JAK2/STAT3 signaling pathway to attract MSC cell recruitment and promote lung cancer metastasis. Our findings offer important insights into how lung cancer metastasis develops in smokers.
Topics: Mice; Animals; Osteopontin; Cigarette Smoking; Lung Neoplasms; Mesenchymal Stem Cells; Signal Transduction; Nicotiana; Neoplastic Processes
PubMed: 36328755
DOI: 10.1016/j.jare.2021.12.011 -
Annals of the New York Academy of... Dec 2017Osteocalcin (OC) and osteopontin (OPN) are major non-collagenous proteins (NCPs) involved in bone matrix organization and deposition. In spite of this, it is currently...
Osteocalcin (OC) and osteopontin (OPN) are major non-collagenous proteins (NCPs) involved in bone matrix organization and deposition. In spite of this, it is currently unknown whether OC and OPN alter bone morphology and consequently affect bone fracture resistance. The goal of this study is to establish the role of OC and OPN in the determination of cortical bone size, shape, and mechanical properties. Our results show that Oc and Opn mice were no different from each other or wild type (WT) with respect to bone morphology (P > 0.1). Bones from mice lacking both NCPs (Oc Opn ) were shorter, with thicker cortices and larger cortical areas, compared with the WT, Oc , and Opn groups (P < 0.05), suggesting a synergistic role for NCPs in the determination of bone morphology. Maximum bending load was significantly different among the groups (P = 0.024), while tissue mineral density and measures of stiffness and strength were not different (P > 0.1). We conclude that the removal of both OC and OPN from bone matrix induces morphological adaptation at the structural level to maintain bone strength.
Topics: Animals; Bone Development; Bone and Bones; Male; Mechanical Phenomena; Mice, Inbred C57BL; Mice, Knockout; Osteocalcin; Osteogenesis; Osteopontin
PubMed: 29044594
DOI: 10.1111/nyas.13470 -
Cancer Epidemiology, Biomarkers &... Jun 2007The use of cancer biomarkers to anticipate the outlines of disease has been an emerging issue, especially as cancer treatment has made such positive steps in the last... (Review)
Review
The use of cancer biomarkers to anticipate the outlines of disease has been an emerging issue, especially as cancer treatment has made such positive steps in the last few years. Progress in the development of consistent malignancy markers is imminent because advances in genomics and bioinformatics have allowed the examination of immense amounts of data. Osteopontin is a phosphorylated glycoprotein secreted by activated macrophages, leukocytes, and activated T lymphocytes, and is present in extracellular fluids, at sites of inflammation, and in the extracellular matrix of mineralized tissues. Several physiologic roles have been attributed to osteopontin, i.e., in inflammation and immune function, in mineralized tissues, in vascular tissue, and in kidney. Osteopontin interacts with a variety of cell surface receptors, including several integrins and CD44. Binding of osteopontin to these cell surface receptors stimulates cell adhesion, migration, and specific signaling functions. Overexpression of osteopontin has been found in a variety of cancers, including breast cancer, lung cancer, colorectal cancer, stomach cancer, ovarian cancer, and melanoma. Moreover, osteopontin is present in elevated levels in the blood and plasma of some patients with metastatic cancers. Therefore, suppression of the action of osteopontin may confer significant therapeutic activity, and several strategies for bringing about this suppression have been identified. This review looks at the recent advances in understanding the possible mechanisms by which osteopontin may contribute functionally to malignancy, particularly in breast cancer. Furthermore, the measurement of osteopontin in the blood or tumors of patients with cancer, as a way of providing valuable prognostic information, will be discussed based on emerging clinical data.
Topics: Animals; Biomarkers, Tumor; Breast Neoplasms; Disease Progression; Female; Gene Expression; Gene Expression Regulation; Humans; Neoplasm Metastasis; Osteopontin
PubMed: 17548669
DOI: 10.1158/1055-9965.EPI-06-1008 -
Nutrients Jan 2024Osteopontin (OPN) is a multifunctional protein that plays a pivotal role in the immune system. It is involved in various biological processes, including cell adhesion,... (Review)
Review
Osteopontin (OPN) is a multifunctional protein that plays a pivotal role in the immune system. It is involved in various biological processes, including cell adhesion, migration and survival. The study of the immunomodulatory effects of OPN is of paramount importance due to its potential therapeutic applications. A comprehensive understanding of how OPN regulates the immune response could pave the way for the development of novel treatments for a multitude of diseases, including autoimmune disorders, infectious diseases and cancer. Therefore, in the following paper, we provide a systematic overview of OPN and its immunoregulatory roles in various diseases, laying the foundation for the development of OPN-based therapies in the future.
Topics: Humans; Osteopontin; Neoplasms; Cell Adhesion; Immunity
PubMed: 38276550
DOI: 10.3390/nu16020312