Osteopontin promotes aromatase expression and estradiol production in human adipocytes

Leitner, Lukas; Jürets, Alexander; Itariu, Bianca; Keck, Maike; Prager, Gerhard; Langer, Felix B.; Grablowitz, Viktor; Zeyda, Maximilian; Stulnig, Thomas M.

doi:10.1007/s10549-015-3603-0

Cited by 10 publications

(8 citation statements)

References 37 publications

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“…Tamoxifen competes with oestrogen for ER-binding, explaining why high levels of oestrogen may reduce the effect of treatment 1 . OPN (cleaved by MMPs) has been shown to induce the expression of aromatase (CYP19A1), an enzyme involved in oestrogen biosynthesis 20 and could thereby contribute to tamoxifen resistance by increasing oestrogen production. Moreover, OPN upregulate multiple genes including INSIG1, CTFG and CYR61.…”

Section: Scorementioning

confidence: 99%

Evaluation of SPP1/osteopontin expression as predictor of recurrence in tamoxifen treated breast cancer

Eremo

Lagergren

Othman

et al. 2020

Sci Rep

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Breast cancer patients treated with tamoxifen may experience recurrence due to endocrine resistance, which highlights the need for additional predictive and prognostic biomarkers. The glyco-phosphoprotein osteopontin (OPN), encoded by the SPP1 gene, has previously shown to be associated with poor prognosis in breast cancer. However, studies on the predictive value of OPN are inconclusive. In the present study, we evaluated tissue SPP1 mRNA and OPN protein expression as markers of recurrence in estrogen receptor-positive (ER+) breast cancer tissue. Tamoxifen-treated patients with recurrence or non-recurrence were selected using a matched case-control design. SPP1 mRNA expression was analysed using qPCR (n = 100) and OPN protein by immunohistochemistry (n = 116) using different antibodies. Odds ratios were estimated with conditional logistic regression. The SPP1 expression increased the risk of recurrence with an odds ratio (OR) of 2.50 (95% confidence interval [CI]; 1.30-4.82), after adjustment for tumour grade, HER 2 status and other treatments to OR 3.62 (95% CI; 1.45-9.07). However, OPN protein expression was not associated with risk of recurrence or with SPP1-gene expression, suggesting SPP1 mRNA a stronger prognostic marker candidate compared to tumor tissue OPN protein.Breast cancer is a heterogeneous disease and the majority of tumours express oestrogen receptors (ER). Patients with ER positive (ER+) breast cancer are candidates for endocrine treatment, such as tamoxifen, although up to 30% of women are expected to experience recurrence due to de novo or acquired tamoxifen resistance 1 . Osteopontin (OPN) is a multifunctional secreted integrin-binding glycoprotein, which has been suggested to have a prognostic value and to be involved in the tamoxifen response 2 . The protein is encoded by the secreted phosphoprotein 1 (SPP1) gene, located on chromosome 4 (4q13). As the SPP1 gene transcript is subject to alternative splicing and the OPN protein to post-translational modifications such as proteolytic processing, glycosylation, tyrosine sulfation and serine/threonine phosphorylation, OPN occurs in several variants. The intracellular variant (iOPN) lacks the N-terminal signal sequence and remains in the cytoplasm. The secreted OPN variants (sOPN) include OPN-a, the full-length protein with a total of 7 exons, and the two splice variants OPN-b and OPN-c, lacking exon 5 (aa 59-72) and 4 (aa 31-57) respectively 3 (Fig. 1). Cleavage by proteases (e.g. thrombin, MMP3 and/or MMP7) produces OPN-N (N-terminal fragment) and OPN-C (C-terminal fragment) 4 . The OPN functions are linked to various physiological and pathological events. Several studies have shown a role of OPN in carcinogenesis, mostly by supporting migratory behaviour in tumour cells and regulating the tumour microenvironment in favour of metastasis 5-9 . In addition, OPN promotes epithelial-mesenchymal transition during metastasis, further indicating an important role in cancer progression 10,11 . The clinical utility is recognized in the CancerSeek test...

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Section: Scorementioning

confidence: 99%

Evaluation of SPP1/osteopontin expression as predictor of recurrence in tamoxifen treated breast cancer

Eremo

Lagergren

Othman

et al. 2020

Sci Rep

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“…Since E2 is mainly converted from TT and other androgens through aromatase, we speculate that the decrease in E2 may be the result of the decrease in precursors. At the same time, the increase in DII may inhibit aromatase activity, because we have observed some suggestive positive associations between DII and TT/E2 in adolescent boys and female adolescents, which may further lead to negative associations with E2 (40,41). However, the assessment of aromatase activity based on the TT/E2 ratio may be inaccurate, and the significant association with TT/E2 may partly be due to changes in E2, making this assumption uncertain.…”

Section: Discussionmentioning

confidence: 83%

Associations Between Dietary Inflammatory Index and Sex Hormones Among 6- to 19-Year-Old Children and Adolescents in NHANES 2015–2016

Zhan

et al. 2022

Front. Endocrinol.

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ObjectivesThis study aimed to assess the relationship between dietary inflammatory index (DII) and sex steroids in children (6-11 years old) and adolescents (12-19 years old) in the U.S. National Health and Nutrition Examination Survey, 2015–2016.MethodsParticipants between the ages of 6-19 have 24-hour dietary intake data, serum sex hormones [total testosterone (TT), estradiol (E2)], and sex hormone-binding globulin (SHBG) available data (n = 1382). The free androgen index (FAI) is calculated as TT divided by SHBG and the ratio of TT to E2 (TT/E2). The constructed puberty state is defined as high levels of steroid hormones (TT≥50 ng/dL in men, E2≥20 pg/ml in women) or onset of menarche. Multiple linear regression analysis was stratified by gender-age and gender-pubertal status groups to evaluate the association between DII and sex hormone levels.ResultsAfter adjusting for covariates, the association between consecutive DII and sex hormone indicators by gender and age group. In male adolescents, DII was always negatively associated with TT (P-trend = 0.09), FAI (P-trend = 0.03) and E2 (P-trend = 0.01), and monotonically positively associated with SHBG (P-trend = 0.02).In female adolescents, with the increase of DII, a significant positive correlation with SHBG was observed (β 0.017, 95%CI: 0.009,0.053) (Table 3). Among female adolescents, a significant negative association between DII and TT and a significant positive association between SHBG were observed in this group. Moreover, DII was positively associated with SHBG of prepubertal males and negatively associated with FAI of prepubertal females.ConclusionsDII was associated with decreased levels of certain sex steroid hormones (TT, FAI, and E2) and increased levels of SHBG in adolescents or pubertal individuals, with the associations presenting somewhat sex-dependent pattern. However, there is little evidence that there is a significant association in children or prepubertal children. Further research needs to be carried out to verify our results.

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“…OPN is an inflammation-dependent gene that is expressed in wound granulation tissue accompanied by the inflammatory response (17). OPN is involved in signal transduction as a secreted chemotactic factor (18,19), depending on the cellular microenvironment.…”

Section: Discussionmentioning

confidence: 99%

Osteopontin improves adhesion and migration of human primary renal cortical epithelial cells during wound healing

Wang

2016

Oncology Letters

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The aim of the present study was to investigate the effect of osteopontin (OPN) on adhesion and migration in human primary renal cortical epithelial cells during wound healing and Transwell assays. MTT assay was used to examine the cell viability and western blot analysis was used to examine the expression of cytoskeletal proteins and cell adhesion molecules. The results showed that overexpression of OPN had positive effects on the viability, proliferation, adhesion and migration of the human primary renal cortical epithelial cells. In addition, the integrity of the cell membrane and cytoskeleton of the epithelial cells was negatively affected by knockdown of OPN expression. The Transwell migration and a wound healing assays performed using OPN-knockdown cells suggested that OPN had a significant impact on cell migration (P=0.0421) and wound healing (P=0.0333). Therefore, OPN may be a potential target for the therapeutic modulation of skin repair to improve the healing rate and quality of wound healing.

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Osteopontin promotes aromatase expression and estradiol production in human adipocytes

Cited by 10 publications

References 37 publications

Evaluation of SPP1/osteopontin expression as predictor of recurrence in tamoxifen treated breast cancer

Evaluation of SPP1/osteopontin expression as predictor of recurrence in tamoxifen treated breast cancer

Associations Between Dietary Inflammatory Index and Sex Hormones Among 6- to 19-Year-Old Children and Adolescents in NHANES 2015–2016

Osteopontin improves adhesion and migration of human primary renal cortical epithelial cells during wound healing

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