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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 1/2015

01-11-2015 | Preclinical study

Osteopontin promotes aromatase expression and estradiol production in human adipocytes

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

Published in: Breast Cancer Research and Treatment | Issue 1/2015

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Abstract

Breast and endometrial cancer are often estrogen dependent, and their incidence and mortality are increased by obesity in postmenopausal women. Osteopontin (OPN) is a cytokine strongly upregulated in adipose tissue (AT) in obesity. OPN function is potentiated by cleavage by matrix metalloproteinases (MMP). OPN and MMPs play a role in cancer development and are prognostic markers in breast cancer progression. While induction of the estrogen-synthesizing enzyme aromatase by TNFa and IL1 has been shown in preadipocytes, an impact of OPN on aromatase expression in AT has not been investigated yet. Gene expression was determined in AT samples of 21 morbidly obese and matched non-obese subjects. Primary human adipocytes were treated with full-length OPN or MMP-cleaved OPN (cOPN). Protein and mRNA expressions were analyzed from cell lysates, or cells were subsequently supplied with testosterone to determine estradiol production and for indirect co-culture with the estrogen-dependent MCF-7 cell line. Aromatase expression strongly correlated with gene expression of OPN and various MMPs in visceral and MMPs in subcutaneous AT, but not with TNFα expression in both tissues. In vitro, cOPN more effectively than full-length OPN upregulated aromatase mRNA in adipocytes and significantly increased aromatase protein level and estradiol production, leading to increased MCF-7 growth in indirect co-culture. OPN and MMPs are upregulated in AT in obesity, and MMP-cleaved OPN is particularly effective in inducing aromatase activity in human adipocytes. Thereby, obesity-induced OPN expression in AT may contribute to estradiol production and thus to the association of obesity with estrogen-dependent cancers.
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Metadata
Title
Osteopontin promotes aromatase expression and estradiol production in human adipocytes
Authors
Lukas Leitner
Alexander Jürets
Bianca K. Itariu
Maike Keck
Gerhard Prager
Felix Langer
Viktor Grablowitz
Maximilian Zeyda
Thomas M. Stulnig
Publication date
01-11-2015
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 1/2015
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-015-3603-0

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