Osteopontin splice variants and polymorphisms in cancer progression and prognosis

Briones-Orta, Marco A.; Avendaño‐Vázquez, S. Eréndira; Aparicio‐Bautista, Diana Ivette; Coombes, Jason D.; Weber, Georg F.; Syn, Wing–Kin

doi:10.1016/j.bbcan.2017.02.005

Cited by 85 publications

(102 citation statements)

References 90 publications

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“…In addition, OPN single nucleotide polymorphisms (SNPs) and OPN variants are explored as a diagnostic target to monitor several immune mediated conditions. Interestingly, recent data show that the production of anti-OPN autoAbs may favour remission in both MS and EAE, which leads to novel strategies, such as vaccination or passive immunization, to boost their levels [11,28,[124][125][126][127].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, two splice variants with deletion of exon 5 (OPN-b) or exon 4 (OPN-c) have been described. Specific combinations of OPN splice variants are associated with distinct malignancies and different stages of cancer development and progression [11,28]. All three forms contain several highly conserved elements including an aspartic rich sequence at the N-terminal and, at the C-terminal, a calcium binding site and a heparin binding domain which is involved in the interaction with certain CD44 variants (v6 and/or v7).…”

Section: Opn Structure and Receptorsmentioning

confidence: 99%

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Role of osteopontin in dendritic cell shaping of immune responses

Prete

Scutera

Sozzani

et al. 2019

Cytokine & Growth Factor Reviews

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Osteopontin (OPN) is a pleiotropic cytokine produced both by immune and non-immune cells and active on different cellular targets. OPN production has been associated with several pathological conditions, including autoimmune diseases (e.g. lupus, multiple sclerosis and rheumatoid arthritis) and cancer. Emerging evidence suggests that the role of OPN has been underestimated, as it seems to be working at multiple levels of immune regulation, such as the shaping of T cell effector responses, the regulation of the tumor microenvironment, and the functional interaction with mesenchymal stromal cells. In this context, dendritic cells (DCs) play a crucial role being both an important source and a cellular target for OPN action. DC family is composed by several cell subsets endowed with specific immune functions. OPN exerts its biological functions through multiple receptors and is produced in different intracellular and secreted forms. OPN production by DC subsets is emerging as a crucial mechanism of regulation in normal and pathological conditions and starts to be exploited as a therapeutic target. This review will focus on the role of DC-derived OPN in shaping immune response and on the complex role of this cytokines in the regulation in immune response.

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Section: Discussionmentioning

confidence: 99%

Section: Opn Structure and Receptorsmentioning

confidence: 99%

Role of osteopontin in dendritic cell shaping of immune responses

Prete

Scutera

Sozzani

et al. 2019

Cytokine & Growth Factor Reviews

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“…OPN is a secreted phosphoglycoprotein and an extracellular matrix constituent 18 . There are five OPN splice variants that encode proteins differing in phosphorylation, transglutamination, secretion, and potentially, activity 19‐21 . OPN is expressed by most immune cells, is a cytokine and a chemoattractant, and activates T‐cells and macrophages 22‐24 .…”

Section: Introductionmentioning

confidence: 99%

Prostatic osteopontin expression is associated with symptomatic benign prostatic hyperplasia

et al. 2020

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Background: Male lower urinary tract symptoms (LUTS) occur in more than half of men above 50 years of age. LUTS were traditionally attributed to benign prostatic hyperplasia (BPH) and therefore the clinical terminology often uses LUTS and BPH interchangeably. More recently, LUTS were also linked to fibrogenic and inflammatory processes. We tested whether osteopontin (OPN), a proinflammatory and profibrotic molecule, is increased in symptomatic BPH. We also tested whether prostate epithelial and stromal cells secrete OPN in response to proinflammatory stimuli and identified downstream targets of OPN in prostate stromal cells. Methods: Immunohistochemistry was performed on prostate sections obtained from the transition zone of patients who underwent surgery (Holmium laser enucleation of the prostate) to relieve LUTS (surgical BPH, S-BPH) or patients who underwent radical prostatectomy to remove low-grade prostate cancer (incidental BPH, I-BPH). Images of stained tissue sections were captured with a Nuance Multispectral Imaging System and histoscore, as a measure of OPN staining intensity, was determined with inForm software. OPN protein abundance was determined by Western blot analysis. The ability of prostate cells to secrete osteopontin in response to IL-1β and TGF-β1 was determined in stromal (BHPrS-1) and epithelial (NHPrE-1 and BHPrE-1) cells by enzyme-linked immunosorbent assay. Quantitative polymerase chain reaction was used to measure gene expression changes in these cells in response to OPN. Results: OPN immunostaining and protein levels were more abundant in S-BPH than I-BPH. Staining was distributed across all cell types with the highest levels in epithelial cells. Multiple OPN protein variants were identified in immortalized prostate stromal and epithelial cells. TGF-β1 stimulated OPN secretion by NHPrE-1 cells and both IL-1β and TGF-β1 stimulated OPN secretion by BHPrS-1 cells. Interestingly, recombinant OPN increased the mRNA expression of CXCL1, CXCL2, CXCL8, PTGS2, and IL6 in BHPrS-1, but not in epithelial cell lines. DK104310; start-up fund provided by the Department of Urology, Case Western Reserve UniversityConclusions: OPN is more abundant in prostates of men with S-BPH compared to men with I-BPH. OPN secretion is stimulated by proinflammatory cytokines, and OPN acts directly on stromal cells to drive the synthesis of proinflammatory mRNAs.Pharmacological manipulation of prostatic OPN may have the potential to reduce LUTS by inhibiting both inflammatory and fibrotic pathways. K E Y W O R D S chemokine, cytokine, fibrosis, prostatic inflammation Tissue collection was approved by the Institutional Review Board at Vanderbilt University Medical Center (VUMC), and analysis of specimens at Case Western Reserve University and the University of Wisconsin-Madison (UW-M). Deidentified prostate tissues were acquired from the VUMC BPH Tissue and Data Biorepository and their 732 | POPOVICS ET AL.

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“…However, the disease relevance of KNG1 levels in patients with LUSC remains to be assessed. Osteopontin (OPN) is expressed in a variety of tissues, and is abundant in body fluids such as blood, milk and urine (10). It is a multifunctional phosphorylated glycoprotein involved in cell migration and adhesion, and mediates the invasion and metastasis of tumor cells (6).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of kininogen 1, osteopontin and α‑1‑antitrypsin in plasma, bronchoalveolar lavage fluid and urine for lung squamous cell carcinoma diagnosis

Wang

Zhang

2020

Oncol Lett

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Lung squamous cell carcinoma (LUSC) progression is accompanied by changes in protein levels that may be reflected in body fluids, such as plasma, bronchoalveolar lavage fluid (BALF) and urine. Certain proteins present in these biofluids can facilitate lung cancer diagnosis. Kininogen 1 (KNG1), osteopontin (OPN) and α-1-antitrypsin (AAT) are associated with tumorigenesis. The present study aimed to explore the combined monitoring of plasma, urine and BALF to gain insight into LUSC by monitoring the levels of the above three protein using ELISA. LUSC (n=31) and healthy controls with benign lung diseases (n=20) were enrolled in the study. KNG1 levels in plasma, BALF and urine were significantly higher in patients with LUSC patients than in controls (P<0.0001, P<0.0001 and P=0.0010, respectively). OPN was upregulated in the plasma and BALF of patients with LUSC relative to controls (P=0.0107 and P=0.0004, respectively), whereas its levels in the urine of healthy controls were significantly higher (P=0.0088). Patients with LUSC had higher AAT levels in plasma, BALF and urine compared with those of the controls (P=0.0022, P=0.0014 and P=0.0005, respectively). Receiver operating characteristic analysis showed an area under the curve (AUC) of 0.81 for KNG1 in plasma, 0.91 in BALF and 0.81 in urine. The AUC for OPN was 0.71 in plasma, 0.83 in BALF and 0.75 in urine. The AUC for AAT was 0.74 in plasma, 0.74 in BALF and 0.86 in urine. Immunohistochemical staining in 20 paired LUSC and adjacent normal tissues showed that KNG1, OPN and AAT levels were higher in LUSC tissues. Therefore, our results showed that KNG1, OPN and AAT in biofluids might be useful for the diagnosis of LUSC. These markers in urine and BALF may be better than in plasma for detecting LUSC.

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Osteopontin splice variants and polymorphisms in cancer progression and prognosis

Cited by 85 publications

References 90 publications

Role of osteopontin in dendritic cell shaping of immune responses

Role of osteopontin in dendritic cell shaping of immune responses

Prostatic osteopontin expression is associated with symptomatic benign prostatic hyperplasia

Evaluation of kininogen 1, osteopontin and α‑1‑antitrypsin in plasma, bronchoalveolar lavage fluid and urine for lung squamous cell carcinoma diagnosis

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