Format

Send to

Choose Destination
Matrix Biol. 2017 Jul;60-61:190-205. doi: 10.1016/j.matbio.2016.11.008. Epub 2016 Nov 29.

Breast cancer-derived extracellular vesicles stimulate myofibroblast differentiation and pro-angiogenic behavior of adipose stem cells.

Author information

1
Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, United States.
2
Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY, United States.
3
Department of Molecular Medicine, Cornell University, Ithaca, NY, United States.
4
Department of Molecular Medicine, Cornell University, Ithaca, NY, United States; Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, United States.
5
Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, United States; Kavli Institute at Cornell for Nanoscale Science, Cornell University, Ithaca, NY, United States. Electronic address: cf99@cornell.edu.

Abstract

Adipose-derived stem cells (ASCs) are abundantly present in the mammary microenvironment and can promote breast cancer malignancy by differentiating into myofibroblasts. However, it remains largely unclear which role tumor-derived extracellular vesicles (TEVs) play in this process. Here, we used microfabricated, type I collagen-based 3-D tissue culture platforms to investigate the effect of breast cancer cell-derived TEVs on ASCs myofibroblast differentiation and consequential changes in extracellular matrix remodeling and vascular sprouting. TEVs collected from MDA MB-231 human metastatic breast cancer cells (MDAs) promoted ASC myofibroblast differentiation in both 2-D and 3-D cultures as indicated by increased alpha smooth muscle actin (α-SMA) and fibronectin (Fn) levels. Correspondingly, TEV-treated ASCs were more contractile, secreted more vascular endothelial growth factor (VEGF), and promoted angiogenic sprouting of human umbilical vein endothelial cells (HUVECs). These changes were dependent on transforming growth factor beta (TGF-β)-related signaling and tumor cell glutaminase activity as their inhibition decreased TEV-related myofibroblastic differentiation of ASCs and related functional consequences. In summary, our data suggest that TEVs are important signaling factors that contribute to ASC desmoplastic reprogramming in the tumor microenvironment, and suggest that tumor cell glutamine metabolism may be used as a therapeutic target to interfere with this process.

KEYWORDS:

Adipose-derived stem cells; Angiogenesis; Extracellular matrix; Fibronectin; Myofibroblast; Tumor microvesicles

PMID:
27913195
PMCID:
PMC5438891
DOI:
10.1016/j.matbio.2016.11.008
[Indexed for MEDLINE]
Free PMC Article

MeSH terms, Substances, Grant support

MeSH terms

Substances

Grant support

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center