Document Detail


Adipocyte-derived endotrophin promotes malignant tumor progression.
MedLine Citation:
PMID:  23041627     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Adipocytes represent a major cell type in the mammary tumor microenvironment and are important for tumor growth. Collagen VI (COL6) is highly expressed in adipose tissue, upregulated in the obese state, and enriched in breast cancer lesions and is a stimulator of mammary tumor growth. Here, we have described a cleavage product of the COL6α3 chain, endotrophin (ETP), which serves as the major mediator of the COL6-mediated tumor effects. ETP augmented fibrosis, angiogenesis, and inflammation through recruitment of macrophages and endothelial cells. Moreover, ETP expression was associated with aggressive mammary tumor growth and high metastatic growth. These effects were partially mediated through enhanced TGF-β signaling, which contributes to tissue fibrosis and epithelial-mesenchymal transition (EMT) of tumor cells. Our results highlight the crucial role of ETP as an obesity-associated factor that promotes tumor growth in the context of adipocyte interactions with tumor and stromal cells.
Authors:
Jiyoung Park; Philipp E Scherer
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-10-08
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  122     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-01     Completed Date:  2013-01-15     Revised Date:  2014-07-02    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4243-56     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Adipocytes / metabolism*,  pathology
Animals
Cell Communication*
Cell Line, Tumor
Collagen Type VI / metabolism*
Endothelial Cells / metabolism,  pathology
Epithelial-Mesenchymal Transition
Female
Fibrosis
Gene Expression Regulation, Neoplastic
Macrophages / metabolism,  pathology
Mammary Neoplasms, Animal / metabolism*,  pathology
Mice
Neoplasm Metastasis
Neoplasm Proteins / metabolism*
Neovascularization, Pathologic / metabolism*,  pathology
Peptide Fragments / metabolism*
Proteolysis*
Stromal Cells / metabolism,  pathology
Transforming Growth Factor beta
Grant Support
ID/Acronym/Agency:
1P30 CA142543-01/CA/NCI NIH HHS; 1S10RR024757/RR/NCRR NIH HHS; DK081182/DK/NIDDK NIH HHS; P01 DK088761/DK/NIDDK NIH HHS; P01-DK088761/DK/NIDDK NIH HHS; P30 CA142543/CA/NCI NIH HHS; R01 CA112023/CA/NCI NIH HHS; R01 DK055758/DK/NIDDK NIH HHS; R01-CA112023/CA/NCI NIH HHS; R01-DK55758/DK/NIDDK NIH HHS; U24 CA126608/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Collagen Type VI; 0/Neoplasm Proteins; 0/Peptide Fragments; 0/Transforming Growth Factor beta; 0/endotrophin
Comments/Corrections

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