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      Overexpression of SPARC correlates with poor prognosis in patients with cervical carcinoma and regulates cancer cell epithelial-mesenchymal transition

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          Abstract

          Secreted protein acidic and rich in cysteine (SPARC) is associated with the progression of numerous types of cancer. However, the role of SPARC in the progression of cervical cancer has not yet been adequately elucidated. In the current study, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry were employed to evaluate the mRNA and protein expression of SPARC in normal cervical tissue, cervical intraepithelial neoplasia (CIN) and cervical cancer. In addition, three epithelial-mesenchymal transition (EMT) markers (E-cadherin, N-cadherin and vimentin) were detected by immunohistochemistry in the same specimens, and an enzyme-linked immunosorbent assay was conducted to detect the serum levels of SPARC in patients with cervical neoplasia. In highly invasive subclones of human cervical carcinoma cells, HeLa-1 and SiHa-1, lentiviral transfections were performed and RT-qPCR and western blot were used to investigate the effects of downregulated EGF-containing fibulin-like extracellular matrix protein 1 on the expression of E-cadherin, N-cadherin and vimentin. The results revealed that, in cervical carcinoma tissue, SPARC expression was significantly upregulated in a manner that positively correlated with N-cadherin and vimentin expression, and negatively correlated with E-cadherin expression. SPARC overexpression and high serum levels were significantly associated with the progression of cervical cancer and adverse prognosis of cervical cancer patients. Downregulation of SPARC can markedly reduce the expression of N-cadherin and vimentin and increase the expression of E-cadherin. Thus, overexpression of SPARC is significantly associated with poor prognostic clinicopathological characteristics in cervical carcinoma, and may be important in EMT. The results of the current study suggest that SPARC may be a potential therapeutic option for individuals diagnosed with cervical carcinoma.

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          Most cited references16

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          Matricellular proteins: extracellular modulators of cell function.

          The term 'matricellular' has been applied to a group of extracellular proteins that do not contribute directly to the formation of structural elements in vertebrates but serve to modulate cell-matrix interactions and cell function. Our understanding of the mode of action of matricellular proteins has been advanced considerably by the recent elucidation of the phenotypes of mice that are deficient in these proteins. In many cases, aspects of these phenotypes have illuminated previously unsuspected consequences of the lack of appropriate interactions of cells with their environment.
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            Osteonectin, a bone-specific protein linking mineral to collagen.

            Osteonectin is a 32,000 dalton bone-specific protein that binds selectively to both hydroxyapatite and collagen. When osteonectin is bound to insolubilized type I collagen, the resultant complex binds synthetic apatite crystals and free calcium ions. The osteonectin-collagen complexes also nucleate mineral phase deposition from metastable balanced salt solutions, Antibodies to osteonectin cross-react with bone and, to a lesser extent, dentin, but not with other tissues. The protein is localized to mineralized bone trabeculae and occurs at higher levels in the matrix than in the cells of bone. These studies suggest that osteonectin is a tissue-specific protein, linking the bone mineral and collagen phases, perhaps initiating active mineralization in normal skeletal tissue.
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              STAT3 and epithelial–mesenchymal transitions in carcinomas

              Cellular programs coupled to cycles of epithelial–mesenchymal transitions (EMTs) play critical roles during embryogenesis, as well as during tissue development, remodeling, and repair. Research over the last decade has established the importance of an ever-expanding list of master EMT transcription factors, whose activity is regulated by STAT3 and function to stimulate the rapid transition of cells between epithelial and mesenchymal phenotypes. Importantly, inappropriate reactivation of embryonic EMT programs in carcinoma cells underlies their metastasis to distant organ sites, as well as their acquisition of stem cell-like and chemoresistant phenotypes operant in eliciting disease recurrence. Thus, targeted inactivation of master EMT transcription factors may offer new inroads to alleviate metastatic disease. Here we review the molecular, cellular, and microenvironmental factors that contribute to the pathophysiological activities of STAT3 during its regulation of EMT programs in human carcinomas.
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                Author and article information

                Journal
                Oncol Lett
                Oncol Lett
                OL
                Oncology Letters
                D.A. Spandidos
                1792-1074
                1792-1082
                May 2016
                31 March 2016
                31 March 2016
                : 11
                : 5
                : 3251-3258
                Affiliations
                [1 ]Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China
                [2 ]Grade 2011, Clinical Medicine, School of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China
                [3 ]Department of Maternal and Child Health Care, School of Public Health, Shandong University, Jinan, Shandong 250012, P.R. China
                Author notes
                Correspondence to: Dr Dehuan Shi, Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, 107 Wenhua Xilu Road, Jinan, Shandong 250012, P.R. China, E-mail: shidehuan2014@ 123456163.com
                Article
                OL-0-0-4399
                10.3892/ol.2016.4399
                4841103
                27123099
                efa459c4-e3ec-499a-b378-eb12c49f0b91
                Copyright: © Shi et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 30 October 2014
                : 16 February 2016
                Categories
                Articles

                Oncology & Radiotherapy
                sparc,cervical carcinoma,prognosis,e-cadherin,n-cadherin,vimentin
                Oncology & Radiotherapy
                sparc, cervical carcinoma, prognosis, e-cadherin, n-cadherin, vimentin

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