Pre- and post-translational regulation of osteopontin in cancer

Osteopontin (OPN) is a matricellular protein that binds to a number of cell surface receptors including integrins and CD44. It is expressed in many tissues and secreted into body fluids including blood, milk and urine. OPN plays important physiological roles in bone remodeling, immune response and inflammation. It is also a tumour-associated protein, and elevated OPN levels are associated with tumour formation, progression and metastasis. Research has revealed a promising role for OPN as a cancer biomarker. OPN is subject to alternative splicing, as well as post-translational modifications such as phosphorylation, glycosylation and proteolytic cleavage. Functional differences have been revealed for different isoforms and post-translational modifications. The pattern of isoform expression and post-translational modification is cell-type specific and may influence the potential role of OPN in malignancy and as a cancer biomarker.     

Regulatory role of osteopontin in malignant transformation of endometrial cancer

Osteopontin (OPN) involves in the tumor-promoting or metastasis in human endometrial cancer. Depletion of OPN gene expression in endometrial cancer cells was significantly decreased in cell viability and the cells undergo apoptotic cell death. The status of OPN in THESC, RL95, Hec1A and Ishikawa cell lines were analyzed by RT-PCR and western blot. After OPN-siRNA transfection, mRNA and protein expression levels of OPN were determined in Hec1A and Ishikawa cells. Cell proliferation and cell cycle distribution were observed by MTT and flow cytometry analysis. DNA fragmentation assay was used to measure cell apoptosis. Cell migration was assessed by wound healing assay. Depletion of OPN gene expression in endometrial cancer cell lines (Hec1A and Ishikawa cells) reproducibly changed their ability of proliferation. Concomitant changes were seen in the expression of OPN binding cell surface receptors, cell cycle-regulatory genes, cell invasion and colony formation nature of the tumor cells. Decreased colonizing potential in the absence of OPN was reversed in the presence of recombinant OPN. Inhibition of anchorage-independent growth was observed in the presence of metabolic inhibitors of the PI3K, Src and integrin signaling cascades, which was ameliorated in the presence of exogenously added OPN. Our result showed the role of OPN in endometrial cancer, in particular on the malignancy-promoting aspects of OPN that may pave way for new approaches to the clinical management of endometrial cancer.     

The role of osteopontin in lung disease

Osteopontin (Opn) is a multifunctional protein independently discovered by investigators from diverse scientific backgrounds and implicated in a broad array of pathological processes. Opn exists both intra- and extracellularly and in numerous pre- and post-translational isoforms. Structurally Opn resembles a matrix protein yet it has well-characterized cytokine like properties including the regulation of cellular migration and cell-mediated immunity. It has thus been classified as both a matricellular protein and a cytokine. Opn is among the most abundantly expressed proteins in a range of lung diseases and has been shown to regulate aspects of pulmonary granuloma formation, fibrosis, and malignancy. Future studies will explore the diagnostic and therapeutic potential of modulating the function of Opn in vivo.     

The emerging role of miR-653 in human cancer

MicroRNAs (miRNAs) refer to a family of non-coding RNA with ~22 nucleotides in length. A high number of studies show evidence that deregulation in miRNAs expression could be implicated in the processes of many pathologies such as cancer, hypoxia, and stroke. Herein, we aimed to summarize the miR-653 expression level and molecular mechanisms through which it functions in human cancer. It was found that variations in miR-653 expression are linked to tumor aggressiveness and unfavorable prognosis in human cancer, and it plays an inhibitory effect in some types of cancer, such as breast, cervical, liver, renal, and lung cancers. In contrast, it plays an acceleratory impact in some other cancers, such as bladder and prostate cancers. In gastric cancer, the role played by miR-653 is still controversial and will need to be elucidated in future studies. Future studies could definitely establish targeting miR-653 as a novel strategy in human cancer, from diagnosis to effective treatment.     

Neurotrophins play an important role in the perineural invasion and distant metastasis of malignant tumor

Neurotrophins (NTs) family was first discovered in nervous system and it regulates the proliferation and differentiation of many neural cell types in the peripheral and central nervous system.Due to their perineural invasive characters, certain part of malignant tumor cases was first diagnosed because of nerve paralysis or idiopathic neuralgia caused by perineural invasion. For this reason, the study on the association between NTs and perineural invasion of malignant tumor aroused the attention of many researchers. Increasing evidence indicates that NTs and their receptors, Trks, play important roles in malignant cells, especially the exhibiting perineural invasive phenotype. It was suggested that NTs produced by neural tissue can act as a chemotactic factor, and tumor cells in which the overexpression of Trks' exists seem to be selected to invade the perineural space. Except for contributing to perineural invasion of malignant tumor, accumulated evidence proved NTs now also significantly associated with the metastasis of malignant tumor. Overexpression of NTs or Trks often correlated with the tumorigenesis, angiogenesis and anoikis resistance in these malignancies, contributing significantly to the metastasis and poor prognosis.In summary, besides its role in development and function of nervous system, NTs also play an important role in the perineural invasion and metastasis of malignant tumor. Considering the role that NTs played in malignant tumor, we believe that further studies between NTs and malignant tumor are necessary. Research on the role of NTs pathway might allow advancements in this field.     

The role of estrogen receptor β (ERβ) in malignant diseases—A new potential target for antiproliferative drugs in prevention and treatment of cancer

The discovery of ERβ in the middle of the 1990s represents a paradigm shift in our understanding of estrogen signaling. It has turned out that estrogen action is not mediated by one receptor, ERα, but by two balancing factors, ERα and ERβ, which are often antagonistic to one another. Excitingly, ERβ has been shown to be widespread in the body and to be involved in a multitude of physiological and pathophysiological events. This has led to a strong interest of the pharmaceutical industry to target ERβ by drugs against various diseases. In this review, focus is on the role of ERβ in malignant diseases where the anti proliferative activity of ERβ gives hope of new therapeutic approaches.     

The role of aquaporin-5 in cancer cell migration: A potential active participant

Emerging data identifies the water channel aquaporin-5 as a major player in multiple cancers. Over-expression of aquaporin-5 has been associated with increased metastasis and poor prognosis, suggesting that aquaporin-5 may enhance cancer cell migration. This review aims to highlight the current knowledge and hypothesis regarding downstream signaling partners of aquaporin-5 in relation to cancer cell migration. The molecular mechanisms that link aquaporin-5 to cell migration are not completely understood. Aquaporin-5 may promote cell movement by increasing water uptake into the front of the cell allowing local swelling. Aquaporin-5 may also activate extracellular-regulated kinases, increasing proliferation and potentially stimulating the migration machinery. Thus, further studies are warranted to identify the underlying mechanisms and signaling pathways. This will reveal whether aquaporin-5 and downstream effectors could be targets for developing new cancer therapeutics.     

The role of cell membrane in the regulation of cell division and malignant transformation

An earlier model in which uptake of essential nutrients for which the cell is auxotrophic, regulates cell division, is discussed in the light of new experimental findings, specifically the purification of a new type of transport-inhibitory protein from rat liver and the properties of the protein. The possible role of such proteins in malignant transformation is also discussed.     

Role of osteopontin in dendritic cell shaping of immune responses

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.     

骨桥蛋白与糖尿病肾病关系的研究进展

骨桥蛋白（OPN）是一种具有细胞粘附和迁移功能的分泌型磷酸化糖蛋白。在肾脏中有广泛分布,研究发现其参与糖尿病肾病（DN）蛋白尿形成、DN的炎症反应及肾脏纤维化过程,抑制OPN可改善糖尿病肾脏病变。     

骨桥蛋白与糖尿病肾病关系的研究进展

骨桥蛋白(OPN)是一种具有细胞粘附和迁移功能的分泌型磷酸化糖蛋白。在肾脏中有广泛分布,研究发现其参与糖尿病肾病(DN)蛋白尿形成、DN的炎症反应及肾脏纤维化过程,抑制OPN可改善糖尿病肾脏病变。     

Tumorigenic properties of alternative osteopontin isoforms in mesothelioma

Osteopontin (SPP1) is an inflammatory cytokine that we previously characterized as a diagnostic marker in patients with asbestos-induced malignant mesothelioma (MM). While SPP1 shows both pro- and anti-tumorigenic biological effects, little is known about the molecular basis of these activities. In this study, we demonstrate that while healthy pleura possesses all three differentially spliced SPP1 isoforms (A-C), in clinical MM specimens isoform A is markedly up-regulated and predominant. To provide a clue to possible functions of the SPP1 isoforms we next performed their functional evaluation via transient expression in MM cell lines. As a result, we report that isoforms A-C demonstrate different activities in cell proliferation, wound closure, and invasion assays. These findings suggest different functions for SPP1 isoforms and underline pro-tumorigenic properties of isoforms A and B.