Obesity-Altered Adipose Stem Cells Promote ER+ Breast Cancer Metastasis through Estrogen Independent Pathways

Autor: Adam Beighley, Paulina Giacomelli, Matthew E. Burow, Rachel M. Wise, Guangdi Wang, Ben A. O’Donnnell, Bruce A. Bunnell, Jacob D. Lampenfeld, Rachel A. Sabol, Brianne N. Sullivan, Melyssa R. Bratton, Margarite D. Matossian, Bridgette M. Collins-Burow, Mark Harrison
Jazyk: angličtina
Rok vydání: 2019
Předmět:
obesity
Estrogen receptor
Adipose tissue
Metastasis
lcsh:Chemistry
Mice
0302 clinical medicine
Cell Movement
Adipocytes
Aromatase
Neoplasm Metastasis
lcsh:QH301-705.5
Spectroscopy
Cells
Cultured
0303 health sciences
biology
Chemistry
Stem Cells
digestive
oral
and skin physiology
General Medicine
Flow Cytometry
3. Good health
Computer Science Applications
Gene Expression Regulation
Neoplastic
Receptors
Estrogen
030220 oncology & carcinogenesis
Female
Stem cell
hormones
hormone substitutes
and hormone antagonists
estrogen receptor
Signal Transduction
medicine.drug_class
Ovariectomy
Breast Neoplasms
Catalysis
Article
Cell Line
Inorganic Chemistry
03 medical and health sciences
breast cancer
medicine
metastasis
Animals
Humans
Physical and Theoretical Chemistry
Molecular Biology
030304 developmental biology
Cell Proliferation
Tumor microenvironment
Organic Chemistry
Estrogens
medicine.disease
adipose stem cells
lcsh:Biology (General)
lcsh:QD1-999
Estrogen
Cancer research
biology.protein
Estrogen receptor alpha
Zdroj: International Journal of Molecular Sciences
Volume 20
Issue 6
International Journal of Molecular Sciences, Vol 20, Iss 6, p 1419 (2019)
ISSN: 1422-0067
Popis: 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 (ER&alpha
) 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 ER&alpha
signaling axis using breast cancer models with constitutively active ER&alpha
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: SERPINE1 and ABCB1. 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.
Databáze: OpenAIRE
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