International journal of molecular sciences, 2019-03, Vol.20 (6), p.1419
2019
Details
- Autor(en) / Beteiligte
- Titel
- Obesity-Altered Adipose Stem Cells Promote ER⁺ Breast Cancer Metastasis through Estrogen Independent Pathways
- Ist Teil von
- International journal of molecular sciences, 2019-03, Vol.20 (6), p.1419
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2019
- Link zum Volltext
- Quelle
- Elektronische Zeitschriftenbibliothek (Open access)
- Beschreibungen/Notizen
- Adipose stem cells (ASCs) play an essential role in tumor microenvironments. These cells are altered by obesity (obASCs) and previous studies have shown that obASCs secrete higher levels of leptin. Increased leptin, which upregulates estrogen receptor alpha (ERα) and aromatase, enhances estrogen bioavailability and signaling in estrogen receptor positive (ER⁺) breast cancer (BC) tumor growth and metastasis. In this study, we evaluate the effect of obASCs on ER⁺BC outside of the ERα signaling axis using breast cancer models with constitutively active ERα resulting from clinically relevant mutations (Y537S and D538G). We found that while obASCs promote tumor growth and proliferation, it occurs mostly through abrogated estrogen signaling when BC has constitutive ER activity. However, obASCs have a similar promotion of metastasis irrespective of ER status, demonstrating that obASC promotion of metastasis may not be completely estrogen dependent. We found that obASCs upregulate two genes in both ER wild type (WT) and ER mutant (MUT) BC: and . This study demonstrates that obASCs promote metastasis in ER WT and MUT xenografts and an ER MUT patient derived xenograft (PDX) model. However, obASCs promote tumor growth only in ER WT xenografts.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1422-0067, 1661-6596eISSN: 1422-0067DOI: 10.3390/ijms20061419Titel-ID: cdi_doaj_primary_oai_doaj_org_article_7679767d3e534c1582232a5926aeada9
- Format
- –
- Schlagworte
- Adipocytes - cytology, adipose stem cells, Angiogenesis, Animals, Body mass index, Body size, Breast cancer, Breast Neoplasms - genetics, Breast Neoplasms - metabolism, CD44 antigen, Cell adhesion & migration, Cell Line, Cell Movement - genetics, Cell Movement - physiology, Cell Proliferation - genetics, Cell Proliferation - physiology, Cells, Cultured, Correlation analysis, CRISPR, estrogen receptor, Estrogen receptors, Estrogens, Estrogens - metabolism, Female, Flow Cytometry, Gene Expression Regulation, Neoplastic - genetics, Genes, Genotype & phenotype, Humans, Intermediates, Kinases, Metabolism, Metastases, Metastasis, Mice, Mutation, Neoplasm Metastasis - genetics, Obesity, Obesity - genetics, Obesity - metabolism, Ovariectomy, Peroxisome proliferator-activated receptors, Post-menopause, Proteins, Pyruvate kinase, Pyruvic acid, Receptors, Estrogen - genetics, Receptors, Estrogen - metabolism, Signal Transduction - genetics, Signal Transduction - physiology, Stem cell transplantation, Stem cells, Stem Cells - cytology, Stem Cells - metabolism, Sterol regulatory element-binding protein, Sterol regulatory element-binding protein 1c, Tumor cells, Tumors, Xenografts, Xenotransplantation